Lithium acetate dihydrate → (11S,11aS)-allyl 11-(tert-butyldimethylsilyloxy)-8-hydroxy-7-methoxy-5-oxo-2-((E)-prop-1-enyl)-11,11a-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10(5H)-carboxylate

HRID 513360Notes

Reaction equation

HRID 513360 reaction equation
O.O.C([O-])(=O)C.[Li+].[Si:8]([O:15][C@@H:16]1[N:22]([C:23]([O:25][CH2:26][CH:27]=[CH2:28])=[O:24])[C:21]2[CH:29]=[C:30]([O:35][Si](C(C)C)(C(C)C)C(C)C)[C:31]([O:33][CH3:34])=[CH:32][C:20]=2[C:19](=[O:46])[N:18]2[CH:47]=[C:48](/[CH:50]=[CH:51]/[CH3:52])[CH2:49][C@@H:17]12)([C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:10])[CH3:9]>CN(C=O)C.C(OCC)(=O)C>[Si:8]([O:15][C@@H:16]1[N:22]([C:23]([O:25][CH2:26][CH:27]=[CH2:28])=[O:24])[C:21]2[CH:29]=[C:30]([OH:35])[C:31]([O:33][CH3:34])=[CH:32][C:20]=2[C:19](=[O:46])[N:18]2[CH:47]=[C:48](/[CH:50]=[CH:51]/[CH3:52])[CH2:49][C@@H:17]12)([C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:9])[CH3:10]

Participants

5

Reactant 2

HCID 23666338Lithium acetate dihydrateHCID 86717767(11S,11aS)-allyl 11-(tert-butyldimethylsilyloxy)-7-methoxy-5-oxo-2-((E)-prop-1-en yl)-8-(triisopropylsilyloxy)-11,11a-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10 (5H)-carboxylate

Product 1

HCID 86717766(11S,11aS)-allyl 11-(tert-butyldimethylsilyloxy)-8-hydroxy-7-methoxy-5-oxo-2-((E)-prop-1-enyl)-11,11a-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10(5H)-carboxylateYield 45%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Lithium acetate dihydrate (0.31 g, 3.04 mmol, 1.0 eq) was added to a solution of the diazepine 11 (2.0 g, 3.04 mmol, 1.0 eq) in wet DMF (20 mL) at 25° C. and stirred for 4 hours. The reaction mixture was diluted with ethyl acetate (200 mL) and washed successively with 0.1M citric acid (50 mL, pH 3), water (50 mL) and brine (10 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, 50/50 v/v n-hexane/EtOAc to 25/75 v/v n-hexane/EtOAc) to afford the product as a pale yellow solid (0.68 g, 45%). LC/MS (3.352 min (ES+)), m/z: 501.1 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 7.02 (s, 1H), 6.66 (m, 1H), 6.53 (s, 1H), 6.03 (d, 1H, J=15.5 Hz), 5.80 (s, 1H), 5.63 (d, 1H, J=8.9 Hz), 5.55 (m, 1H), 5.29 (m, 1H), 4.87 (m, 2H), 4.39 (dd, 1H, J=13.5, 4.2 Hz), 4.20 (dd, 1H, J=13.2, 5.7 Hz), 3.73 (s, 3H), 3.59 (m, 1H), 2.81 (dd, 1H, J=16.1, 10.5 Hz), 2.35 (d, 1H, J=15.7 Hz), 1.61 (d, 3H, J=6.4 Hz), 0.67 (s, 9H), 0.05 (s, 3H), 0.00 (s, 3H).

Workup

  1. washwashed successively with 0.1M citric acid (50 mL, pH 3), water (50 mL) and brine (10 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash chromatography (silica gel, 50/50 v/v n-hexane/EtOAc to 25/75 v/v n-hexane/EtOAc)

Sources & evidence

ORD record
ord-367fa8758ef04307a96af80502673fbd
Source dataset
uspto-grants-2015_08
Patent number
US09102704B2

Reaction notes

Loading…