Sodium Bicarbonate → chloromethyl methyl (3S,3aS,6R,6aS)-6-(nitrooxy)hexahydrofuro[3,2-b]furan-3-yl phosphate

HRID 384579Notes

Reaction equation

C(=O)(O)[O-].[Na+].[P:6](O)([O:10][C@H:11]1[CH2:15][O:14][C@@H:13]2[C@H:16]([O:19][N+:20]([O-:22])=[O:21])[CH2:17][O:18][C@H:12]12)([O:8][CH3:9])=[O:7].S(Cl)([O:27][CH2:28][Cl:29])(=O)=O>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.ClCCl.O>[P:6]([O:10][C@H:11]1[CH2:15][O:14][C@@H:13]2[C@H:16]([O:19][N+:20]([O-:22])=[O:21])[CH2:17][O:18][C@H:12]12)([O:8][CH3:9])([O:27][CH2:28][Cl:29])=[O:7]

Participants

Conditions

Temperature: 0 °C

Procedure

Sodium bicarbonate (289 mg, 3.44 mmol) followed by tetrabutylammonium hydrogensulfate (29.2 mg, 0.086 mmol) were added to a vigorously stirred 0° C. mixture of methyl (3S,3aS,6R,6aS)-6-(nitrooxy)hexahydrofuro[3,2-b]furan-3-yl hydrogen phosphate (245 mg, 0.859 mmol) in dichloromethane (5 mL) and water (7.5 mL), and the mixture was stirred at 0° C. for 10 minutes. Chloromethyl chlorosulfate (0.106 mL, 1.03 mmol) in dichloromethane (2.5 mL) was added, and the mixture was stirred at room temperature for overnight. The organic phase was removed, dried and concentrated. Chromatography over silica, eluting with 20-60% ethyl acetate/hexane afforded the title compound as a colorless oil. 1H NMR (500 MHz, CDCl3) δ 5.72-5.64 (m, 2H), 5.36 (td, J=5.5, 2.8 Hz, 1H), 5.02 (t, J=5.2 Hz, 1H), 4.93 (quintet, J=3.6 Hz, 1H), 4.63 (dd, J=12.1, 4.8 Hz, 1H), 4.18 (dd, J=11.0, 7.3 Hz, 1H), 4.00 (dd, J=11.4, 2.8 Hz, 1H), 3.94 (dq, J=11.1, 2.4 Hz, 1H), 3.90 (dd, J=11.3, 5.6 Hz, 1H), 3,83 (d, J=11.4 Hz, 3H); LC-MS: m/z 334.0 (M+H).

Workup

stirringthe mixture was stirred at room temperature for overnight
customThe organic phase was removed
customdried
concentrationconcentrated
washChromatography over silica, eluting with 20-60% ethyl acetate/hexane

Sources & evidence

ORD record: ord-ce415d1e93c042848c29a4d97e14c6e7
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08367711B2

Reaction notes

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