Cesium carbonate → (3R,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-[4-(2-amino-2-oxoethoxy)benzyl]-3-[(1,3-benzodioxol-5-ylsulfonyl)(isobutyl)amino]-2-hydroxypropylcarbamate

HRID 1253978Notes

Reaction equation

HRID 1253978 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([S:10]([N:13]([CH2:38][CH:39]([CH3:41])[CH3:40])[CH2:14][C@@H:15]([OH:37])[C@@H:16]([NH:25][C:26](=[O:36])[O:27][C@@H:28]3[C@H:35]4[C@H:31]([O:32][CH2:33][CH2:34]4)[O:30][CH2:29]3)[CH2:17][C:18]3[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=3)(=[O:12])=[O:11])=[CH:9][C:4]=2[O:3][CH2:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:49][C:50]([NH2:52])=[O:51]>CN(C)C=O.C(OCC)(=O)C>[NH2:52][C:50](=[O:51])[CH2:49][O:24][C:21]1[CH:22]=[CH:23][C:18]([CH2:17][C@H:16]([NH:25][C:26](=[O:36])[O:27][C@@H:28]2[C@H:35]3[C@H:31]([O:32][CH2:33][CH2:34]3)[O:30][CH2:29]2)[C@H:15]([OH:37])[CH2:14][N:13]([S:10]([C:8]2[CH:7]=[CH:6][C:5]3[O:1][CH2:2][O:3][C:4]=3[CH:9]=2)(=[O:12])=[O:11])[CH2:38][CH:39]([CH3:41])[CH3:40])=[CH:19][CH:20]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 696322-BromoacetamideHCID 59997191(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-3-[(1,3-benzodioxol-5-ylsulfonyl) (isobutyl)amino]-2-hydroxy-1-(4-hydroxybenzyl)propylcarbamate

Product 1

HCID 59997192(3R,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-[4-(2-amino-2-oxoethoxy)benzyl]-3-[(1,3-benzodioxol-5-ylsulfonyl)(isobutyl)amino]-2-hydroxypropylcarbamateYield 86.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-3-[(1,3-benzodioxol-5-ylsulfonyl) (isobutyl)amino]-2-hydroxy-1-(4-hydroxybenzyl)propylcarbamate (47 mg, 0.08 mmol) in anhydrous dimethylformamide (2 mL) was added cesium carbonate (78 mg, 0.24 mmol) and 2-bromoacetamide (22 mg, 0.16 mmol). After 1 h at ambient temperature, the mixture was diluted with ethyl acetate, washed with water (3×), brine, dried (sodium sulfate), and evaporated. The residue was purified by chromatography (silica gel, dichloromethane/methanol, 97:3) to afford the title product as a white solid (45 mg) 1H NMR (DMSO-d6): δ 0.78 (3H, d), 0.82 (3H, d), 1.2 (1H, dd), 1.4 (1H, quintuplet), 1.9-2.0 (1H, m), 2.35 (1H, t), 2.6-2.8 (3H, m), 2.9 (1H, d), 2.95 (1H, dd), 3.25-3.30 (1H, m), 3.45 (1H, br s), 3.5-3.6 (3H, m), 3.7 (1H, t), 3.8 (1H, dd), 4.3 (2H, s), 4.8 (1H, dt), 5.0 (1H, d), 5.5 (1H, d), 6.18 (2H, s), 6.8 (2H, d), 7.0-7.15 (3H, m), 7.22 (1H, s), 7.24 (1H, d), 7.26 (1H, d), 7.32 (1H, s), 7.42 (1H, s); MS: 650 (MH+)

Workup

  1. washwashed with water (3×), brine
  2. dry with materialdried (sodium sulfate)
  3. customevaporated
  4. customThe residue was purified by chromatography (silica gel, dichloromethane/methanol, 97:3)

Sources & evidence

ORD record
ord-1796cfefffcf4fa783d9ae7e10138c6c
Source dataset
uspto-grants-2013_06
Patent number
US08455497B2

Reaction notes

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