Dimethylformamide → (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-{4-[(3-cyanobenzyl)oxy]benzyl}-3-[(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)(isobutyl)amino]-2-hydroxypropylcarbamate

HRID 1253995Notes

Reaction equation

HRID 1253995 reaction equation
[O:1]1[C:6]2[CH:7]=[CH:8][C:9]([S:11]([N:14]([CH2:39][CH:40]([CH3:42])[CH3:41])[CH2:15][C@@H:16]([OH:38])[C@@H:17]([NH:26][C:27](=[O:37])[O:28][C@@H:29]3[C@H:36]4[C@H:32]([O:33][CH2:34][CH2:35]4)[O:31][CH2:30]3)[CH2:18][C:19]3[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][CH:20]=3)(=[O:13])=[O:12])=[CH:10][C:5]=2[O:4][CH2:3][CH2:2]1.[C:43]([C:45]1[CH:46]=[C:47]([CH:50]=[CH:51][CH:52]=1)[CH2:48]Cl)#[N:44].C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)C=O>C(OCC)(=O)C>[C:43]([C:45]1[CH:46]=[C:47]([CH:50]=[CH:51][CH:52]=1)[CH2:48][O:25][C:22]1[CH:21]=[CH:20][C:19]([CH2:18][C@H:17]([NH:26][C:27](=[O:37])[O:28][C@@H:29]2[C@H:36]3[C@H:32]([O:33][CH2:34][CH2:35]3)[O:31][CH2:30]2)[C@H:16]([OH:38])[CH2:15][N:14]([S:11]([C:9]2[CH:8]=[CH:7][C:6]3[O:1][CH2:2][CH2:3][O:4][C:5]=3[CH:10]=2)(=[O:12])=[O:13])[CH2:39][CH:40]([CH3:42])[CH3:41])=[CH:24][CH:23]=1)#[N:44]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 5221263-(Chloromethyl)benzonitrileHCID 60097306HCID 60097306, compound

Product 1

HCID 59997349(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-{4-[(3-cyanobenzyl)oxy]benzyl}-3-[(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)(isobutyl)amino]-2-hydroxypropylcarbamateYield 34.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

49 mg of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-3-[(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)(isobutyl)amino]-2-hydroxy-1-(4-hydroxy benzyl)propylcarbamate, 20 mg of m-cyanobenzylchloride, 20 mg of cesium carbonate and 0.5 ml of dimethyl formamide were stirred at rt for 5 h. The mixture was diluted with ethyl acetate and extracted with water. Chromatography on silica gel (1:1 ethylacetate/hexane) gave the title compound as a white solid (20 mg). 1H NMR: 0.87 (6H, dd), 1.58 (2H, m), 1.8 (1H, m), 2.75 (2H, m), 2.9 (4H, m), 3.1 (1H, m), 3.62 (3H, m), 3.8 (3H, m), 3.95 (1H, m), 4.25 (4H, m), 4.95 (2H, m), 5.0 (2H, s), 5.62 (1H, d), 6.82 (2H, d), 6.92 (1H, d), 7.1 (2H, d), 7.2 (2H, m), 7.45 (1H, t), 7.6 (2H, m), 7.75 (1H, s). MS:722(M+H)

Workup

  1. extractionextracted with water

Sources & evidence

ORD record
ord-dda0c60d540b480eb34579f0850117e4
Source dataset
uspto-grants-2013_06
Patent number
US08455497B2

Reaction notes

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