5-Fluoro-1-[(4S,5R)-5-(2-hydroxy-ethyl)-2,2-dimethyl-1,3-dioxolan-4-yl]pyrimidine-2,4(1H,3H)-dione.

In the title compound, C(11)H(15)FN(2)O(5), the five-membered ring has an envelope conformation, while the six-membered ring is essentially planar, with a maximum deviation of 0.032 (2) Å from the mean plane. The crystal packing is stabilized by inter-molecular N-H⋯O and O-H⋯O hydrogen bonds, generating a layer structure parallel to (001).

Related literature

For applications of modified nucleosides in medical chemistry, see: Huryn & Okabe (1992 ▶); Minuk et al. (1992 ▶); Luscombe et al. (1996 ▶); Korba & Boyd (1996 ▶). For the synthesis, see: Valdivia et al. (2005 ▶); Xie et al. (1996 ▶). For ring conformation analysis, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C11H15FN2O5

M = 274.25

Monoclinic,

a = 20.8905 (8) Å

b = 5.5751 (1) Å

c = 13.5639 (5) Å

β = 126.297 (6)°

V = 1273.21 (12) Å3

Z = 4

Cu Kα radiation

μ = 1.06 mm−1

T = 298 K

0.40 × 0.12 × 0.08 mm

Data collection

Oxford Diffraction Gemini Atlas CCD diffractometer

Absorption correction: analytical (CrysAlis RED; Oxford Diffraction, 2009 ▶) T min = 0.885, T max = 0.964

4606 measured reflections

1786 independent reflections

1732 reflections with I > 2σ(I)

R int = 0.013

Refinement

R[F 2 > 2σ(F 2)] = 0.027

wR(F 2) = 0.071

S = 1.04

1786 reflections

181 parameters

1 restraint

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.23 e Å−3

Δρmin = −0.20 e Å−3

Absolute structure: Flack (1983 ▶), 498 Friedel pairs

Flack parameter: 0.0 (2)

Data collection: CrysAlis CCD (Oxford Diffraction, 2009 ▶); cell refinement: CrysAlis RED (Oxford Diffraction, 2009 ▶); data reduction: CrysAlis RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810016065/is2543sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810016065/is2543Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C11H15FN2O5	F(000) = 576
Mr = 274.25	Dx = 1.431 Mg m−3
Monoclinic, C2	Cu Kα radiation, λ = 1.54184 Å
Hall symbol: C 2y	Cell parameters from 4215 reflections
a = 20.8905 (8) Å	θ = 4.0–68.0°
b = 5.5751 (1) Å	µ = 1.06 mm−1
c = 13.5639 (5) Å	T = 298 K
β = 126.297 (6)°	Prism, colorless
V = 1273.21 (12) Å3	0.40 × 0.12 × 0.08 mm
Z = 4

Oxford Diffraction Gemini Atlas CCD diffractometer	1786 independent reflections
Radiation source: fine-focus sealed tube	1732 reflections with I > 2σ(I)
graphite	Rint = 0.013
Detector resolution: 10.4685 pixels mm-1	θmax = 68.1°, θmin = 4.0°
ω scans	h = −22→24
Absorption correction: analytical (CrysAlis RED; Oxford Diffraction, 2009)	k = −4→6
Tmin = 0.885, Tmax = 0.964	l = −16→16
4606 measured reflections

Refinement on F2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.027	w = 1/[σ2(Fo2) + (0.038P)2 + 0.4768P] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.071	(Δ/σ)max < 0.001
S = 1.04	Δρmax = 0.23 e Å−3
1786 reflections	Δρmin = −0.19 e Å−3
181 parameters	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
1 restraint	Extinction coefficient: 0.0075 (4)
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack (1983), 498 Friedel pairs
Secondary atom site location: difference Fourier map	Flack parameter: 0.0 (2)

Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

	x	y	z	Uiso*/Ueq
O1	0.69200 (8)	0.0051 (3)	0.95722 (12)	0.0519 (4)
N1	0.66380 (8)	0.2920 (3)	0.81679 (12)	0.0339 (3)
O4	0.72382 (7)	0.3751 (3)	0.65042 (11)	0.0438 (3)
F1	0.52029 (9)	0.7673 (3)	0.69645 (15)	0.0816 (5)
O5	0.90402 (9)	0.7069 (3)	0.88915 (13)	0.0478 (4)
O2	0.49424 (9)	0.5250 (3)	0.84757 (15)	0.0627 (5)
C5	0.72230 (11)	0.1894 (4)	0.80156 (17)	0.0403 (4)
H5	0.7609	0.0950	0.8745	0.048*
N2	0.59707 (9)	0.2801 (4)	0.90550 (15)	0.0434 (4)
C1	0.61955 (10)	0.4901 (4)	0.75175 (16)	0.0418 (4)
H1	0.6291	0.5673	0.7009	0.050*
O3	0.68552 (11)	0.0402 (3)	0.69943 (16)	0.0681 (5)
C4	0.65428 (10)	0.1784 (4)	0.89752 (15)	0.0362 (4)
C6	0.76688 (9)	0.3754 (4)	0.78102 (14)	0.0350 (4)
H6	0.7625	0.5332	0.8084	0.042*
C2	0.56349 (11)	0.5732 (4)	0.76007 (18)	0.0466 (5)
C3	0.54650 (10)	0.4653 (4)	0.83818 (17)	0.0435 (5)
C8	0.89973 (11)	0.4915 (4)	0.83002 (18)	0.0469 (5)
H8A	0.9528	0.4318	0.8649	0.056*
H8B	0.8733	0.5206	0.7435	0.056*
C7	0.85368 (10)	0.3099 (4)	0.84748 (17)	0.0437 (5)
H7A	0.8779	0.2948	0.9342	0.052*
H7B	0.8572	0.1551	0.8184	0.052*
C9	0.68429 (13)	0.1521 (4)	0.60232 (19)	0.0533 (6)
C10	0.72705 (17)	−0.0147 (5)	0.5721 (2)	0.0689 (7)
H10A	0.6979	−0.1621	0.5400	0.103*
H10B	0.7793	−0.0473	0.6448	0.103*
H10C	0.7313	0.0588	0.5121	0.103*
C11	0.60061 (17)	0.2034 (8)	0.4934 (3)	0.1094 (13)
H11A	0.5725	0.0550	0.4592	0.164*
H11B	0.6016	0.2893	0.4330	0.164*
H11C	0.5743	0.2986	0.5185	0.164*
H1N	0.5950 (12)	0.236 (5)	0.9622 (19)	0.048 (6)*
H1O	0.9348 (15)	0.789 (6)	0.896 (2)	0.072 (9)*

	U11	U22	U33	U12	U13	U23
O1	0.0606 (7)	0.0506 (9)	0.0586 (7)	0.0216 (7)	0.0430 (7)	0.0239 (8)
N1	0.0336 (6)	0.0365 (9)	0.0345 (7)	0.0036 (7)	0.0218 (6)	0.0044 (6)
O4	0.0520 (7)	0.0397 (8)	0.0390 (6)	−0.0028 (6)	0.0265 (5)	0.0009 (6)
F1	0.0799 (8)	0.0748 (11)	0.1109 (11)	0.0463 (8)	0.0678 (8)	0.0532 (10)
O5	0.0529 (8)	0.0445 (10)	0.0622 (8)	−0.0061 (7)	0.0430 (7)	−0.0071 (7)
O2	0.0621 (8)	0.0584 (11)	0.0954 (11)	0.0167 (8)	0.0619 (8)	0.0137 (10)
C5	0.0465 (9)	0.0352 (11)	0.0509 (9)	0.0048 (9)	0.0353 (8)	0.0038 (9)
N2	0.0502 (8)	0.0455 (10)	0.0498 (8)	0.0083 (8)	0.0381 (7)	0.0092 (8)
C1	0.0410 (8)	0.0437 (12)	0.0447 (9)	0.0064 (9)	0.0275 (7)	0.0138 (9)
O3	0.1087 (12)	0.0487 (10)	0.0938 (11)	−0.0334 (9)	0.0857 (10)	−0.0292 (9)
C4	0.0368 (8)	0.0390 (11)	0.0359 (8)	0.0011 (8)	0.0232 (7)	0.0018 (8)
C6	0.0397 (8)	0.0320 (10)	0.0388 (8)	0.0022 (8)	0.0263 (7)	0.0006 (8)
C2	0.0444 (9)	0.0382 (12)	0.0563 (11)	0.0122 (9)	0.0294 (9)	0.0139 (9)
C3	0.0417 (8)	0.0401 (12)	0.0557 (10)	0.0025 (9)	0.0326 (8)	0.0013 (9)
C8	0.0430 (9)	0.0492 (13)	0.0608 (11)	0.0008 (10)	0.0374 (9)	−0.0079 (11)
C7	0.0400 (9)	0.0402 (12)	0.0531 (10)	0.0056 (9)	0.0288 (8)	0.0001 (9)
C9	0.0641 (12)	0.0483 (14)	0.0551 (11)	−0.0145 (11)	0.0394 (10)	−0.0142 (10)
C10	0.1132 (18)	0.0523 (16)	0.0761 (14)	−0.0072 (15)	0.0752 (15)	−0.0113 (13)
C11	0.0695 (16)	0.110 (3)	0.086 (2)	−0.0123 (19)	0.0121 (15)	−0.043 (2)

O1—C4	1.206 (2)	O3—C9	1.444 (3)
N1—C1	1.373 (3)	C6—C7	1.516 (2)
N1—C4	1.378 (2)	C6—H6	0.9800
N1—C5	1.471 (2)	C2—C3	1.434 (3)
O4—C9	1.419 (3)	C8—C7	1.509 (3)
O4—C6	1.435 (2)	C8—H8A	0.9700
F1—C2	1.345 (2)	C8—H8B	0.9700
O5—C8	1.417 (3)	C7—H7A	0.9700
O5—H1O	0.75 (3)	C7—H7B	0.9700
O2—C3	1.218 (2)	C9—C11	1.504 (4)
C5—O3	1.393 (3)	C9—C10	1.505 (3)
C5—C6	1.526 (3)	C10—H10A	0.9600
C5—H5	0.9800	C10—H10B	0.9600
N2—C3	1.369 (3)	C10—H10C	0.9600
N2—C4	1.384 (2)	C11—H11A	0.9600
N2—H1N	0.83 (2)	C11—H11B	0.9600
C1—C2	1.325 (3)	C11—H11C	0.9600
C1—H1	0.9300
C1—N1—C4	121.43 (14)	N2—C3—C2	112.25 (16)
C1—N1—C5	121.47 (14)	O5—C8—C7	108.20 (15)
C4—N1—C5	117.10 (15)	O5—C8—H8A	110.1
C9—O4—C6	109.72 (14)	C7—C8—H8A	110.1
C8—O5—H1O	110 (2)	O5—C8—H8B	110.1
O3—C5—N1	110.92 (16)	C7—C8—H8B	110.1
O3—C5—C6	105.14 (14)	H8A—C8—H8B	108.4
N1—C5—C6	114.14 (16)	C8—C7—C6	113.23 (17)
O3—C5—H5	108.8	C8—C7—H7A	108.9
N1—C5—H5	108.8	C6—C7—H7A	108.9
C6—C5—H5	108.8	C8—C7—H7B	108.9
C3—N2—C4	128.17 (16)	C6—C7—H7B	108.9
C3—N2—H1N	113.4 (16)	H7A—C7—H7B	107.7
C4—N2—H1N	118.1 (16)	O4—C9—O3	105.54 (16)
C2—C1—N1	121.28 (17)	O4—C9—C11	107.9 (2)
C2—C1—H1	119.4	O3—C9—C11	111.2 (2)
N1—C1—H1	119.4	O4—C9—C10	112.88 (19)
C5—O3—C9	110.51 (16)	O3—C9—C10	106.8 (2)
O1—C4—N1	123.91 (16)	C11—C9—C10	112.5 (2)
O1—C4—N2	121.80 (16)	C9—C10—H10A	109.5
N1—C4—N2	114.29 (16)	C9—C10—H10B	109.5
O4—C6—C7	112.88 (14)	H10A—C10—H10B	109.5
O4—C6—C5	102.72 (13)	C9—C10—H10C	109.5
C7—C6—C5	111.86 (15)	H10A—C10—H10C	109.5
O4—C6—H6	109.7	H10B—C10—H10C	109.5
C7—C6—H6	109.7	C9—C11—H11A	109.5
C5—C6—H6	109.7	C9—C11—H11B	109.5
C1—C2—F1	121.20 (18)	H11A—C11—H11B	109.5
C1—C2—C3	122.28 (19)	C9—C11—H11C	109.5
F1—C2—C3	116.51 (17)	H11A—C11—H11C	109.5
O2—C3—N2	121.46 (18)	H11B—C11—H11C	109.5
O2—C3—C2	126.3 (2)
C1—N1—C5—O3	−82.0 (2)	N1—C5—C6—C7	141.06 (16)
C4—N1—C5—O3	96.83 (19)	N1—C1—C2—F1	179.91 (19)
C1—N1—C5—C6	36.5 (2)	N1—C1—C2—C3	1.0 (3)
C4—N1—C5—C6	−144.63 (16)	C4—N2—C3—O2	173.9 (2)
C4—N1—C1—C2	−3.0 (3)	C4—N2—C3—C2	−6.5 (3)
C5—N1—C1—C2	175.8 (2)	C1—C2—C3—O2	−177.1 (2)
N1—C5—O3—C9	107.78 (18)	F1—C2—C3—O2	4.0 (3)
C6—C5—O3—C9	−16.1 (2)	C1—C2—C3—N2	3.3 (3)
C1—N1—C4—O1	−179.53 (18)	F1—C2—C3—N2	−175.64 (18)
C5—N1—C4—O1	1.6 (3)	O5—C8—C7—C6	67.2 (2)
C1—N1—C4—N2	0.4 (3)	O4—C6—C7—C8	65.3 (2)
C5—N1—C4—N2	−178.50 (15)	C5—C6—C7—C8	−179.47 (16)
C3—N2—C4—O1	−175.3 (2)	C6—O4—C9—O3	15.2 (2)
C3—N2—C4—N1	4.8 (3)	C6—O4—C9—C11	134.1 (2)
C9—O4—C6—C7	96.42 (19)	C6—O4—C9—C10	−101.1 (2)
C9—O4—C6—C5	−24.21 (19)	C5—O3—C9—O4	1.4 (2)
O3—C5—C6—O4	24.16 (19)	C5—O3—C9—C11	−115.3 (2)
N1—C5—C6—O4	−97.61 (16)	C5—O3—C9—C10	121.8 (2)
O3—C5—C6—C7	−97.17 (18)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H1N···O5i	0.83 (2)	2.01 (2)	2.828 (2)	167 (3)
O5—H1O···O2ii	0.75 (3)	2.16 (3)	2.876 (2)	160 (3)

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H1N⋯O5i	0.83 (2)	2.01 (2)	2.828 (2)	167 (3)
O5—H1O⋯O2ii	0.75 (3)	2.16 (3)	2.876 (2)	160 (3)

Symmetry codes: (i) ; (ii) .