Trimethyl phosphite → dimethyl (3S,3aS,6R,6aS)-6-(nitrooxy)hexahydrofuro[3,2-b]furan-3-yl phosphate

HRID 222536

Reaction equation

HRID 222536 reaction equation
[P:1]([O:6]C)([O:4][CH3:5])[O:2][CH3:3].[CH2:8]1[O:12][C@@H:11]2[C@H:13]([O:16][N+:17]([O-:19])=[O:18])[CH2:14][O:15][C@@H:10]2[C@H:9]1[OH:20].C(Br)(Br)(Br)Br>N1C=CC=CC=1>[P:1]([O:20][C@H:9]1[CH2:8][O:12][C@@H:11]2[C@H:13]([O:16][N+:17]([O-:19])=[O:18])[CH2:14][O:15][C@H:10]12)([O:4][CH3:5])([O:2][CH3:3])=[O:6]

Participants

5

Reactant 3

HCID 8472Trimethyl phosphiteHCID 11205Carbon tetrabromideHCID 27661Isosorbide Mononitrate

Product 1

HCID 86652099dimethyl (3S,3aS,6R,6aS)-6-(nitrooxy)hexahydrofuro[3,2-b]furan-3-yl phosphate

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Trimethyl phosphite (2.95 mL, 25.0 mmol) was added dropwise over ca. 1 hour to a stirred 0° C. mixture of isosorbide-5-mononitrate (3.82 g, 20.0 mmol) and carbon tetrabromide (7.30 g, 22.0 mmol) in pyridine (10 mL), and the mixture was stirred at room temperature for 3 hours. The reaction was partitioned between 1M hydrochloric acid and diethyl ether/ethyl acetate (1:1). The aqueous phase was extracted with diethyl ether. The combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate and brine, dried (sodium sulfate), filtered and concentrated in vacuo. Chromatography over silica eluting with 50-100% ethyl acetate/hexane afforded the title compound as an orange solid. 1H NMR (500 MHz, CD3OD) δ 5.46 (td, J=5.5, 2.2 Hz, 1H), 5.02 (t, J=5.3 Hz, 1H), 4.82 (dd, J=6.8, 2.7 Hz, 1H), 4.58 (d, J=5.1 Hz, 1H), 4.10 (d, J=10.7 Hz, 1H), 3.99 (dd, J=11.5, 2.1 Hz, 1H), 3.91 (dd, J=11.4, 5.2 Hz, 1H), 3.88 (dt, J=11.0, 2.4 Hz, 1H), 3.80 (d, J=2.7 Hz, 3H), 3.78 (d, J=2.7 Hz, 3H); LC-MS: m/z 300.0 (M+H).

Workup

  1. customThe reaction was partitioned between 1M hydrochloric acid and diethyl ether/ethyl acetate (1:1)
  2. extractionThe aqueous phase was extracted with diethyl ether
  3. washThe combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate and brine
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-848f1bfb7463414c81c8f9c0afce36d7
Source dataset
uspto-grants-2012_06
Patent number
US08207208B2

Linked notes

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