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

HRID 222538Notes

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-df771f6cfde6455bb2c2829d401b9f94
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08207208B2

Reaction notes

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