Potassium Carbonate → Di-tert-butyl (1R,2R,3S,4S,5R,6R)-2-(tert-butoxycarbonylamino)-3-[(3,4-dichlorophenyl)methoxy]-4-[(2-methyl-1,2,4-triazol-3-yl)sulfanyl]bicyclo[3.1.0]hexane-2,6-dicarboxylate

HRID 2172997Notes

Reaction equation

HRID 2172997 reaction equation
[CH3:1][N:2]1[C:6](=[S:7])[N:5]=[CH:4][NH:3]1.C(=O)([O-])[O-].[K+].[K+].[C:14]([O:18][C:19]([NH:21][C@@:22]1([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[C@H:27]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][C:33]([Cl:36])=[C:32]([Cl:37])[CH:31]=2)[C@H:26](OS(C)(=O)=O)[C@@H:25]2[C@H:23]1[C@H:24]2[C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])=[O:20])([CH3:17])([CH3:16])[CH3:15]>CN(C)C=O.[Cl-].[Na+].O>[C:14]([O:18][C:19]([NH:21][C@@:22]1([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[C@H:27]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][C:33]([Cl:36])=[C:32]([Cl:37])[CH:31]=2)[C@@H:26]([S:7][C:6]2[N:2]([CH3:1])[N:3]=[CH:4][N:5]=2)[C@@H:25]2[C@H:23]1[C@H:24]2[C:43]([O:45][C:46]([CH3:48])([CH3:47])[CH3:49])=[O:44])=[O:20])([CH3:17])([CH3:15])[CH3:16]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 30381873H-1,2,4-Triazole-3-thione, 1,2-dihydro-2-methyl-HCID 86695975Di-tert-butyl (1S,2R,3S,4R,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-[(3,4-dichlorobenzyl)oxy]-4-[(methylsulfonyl)oxy]bicyclo[3.1.0]hexane-2,6-dicarboxylate

Product 1

HCID 67708365Di-tert-butyl (1R,2R,3S,4S,5R,6R)-2-(tert-butoxycarbonylamino)-3-[(3,4-dichlorophenyl)methoxy]-4-[(2-methyl-1,2,4-triazol-3-yl)sulfanyl]bicyclo[3.1.0]hexane-2,6-dicarboxylateYield 100%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
80 °C

Procedure

Add 2-methyl-1H-1,2,4-triazole-3-thione (0.126 g, 1.09 mmol) and potassium carbonate (0.35 g, 2.52 mmol) to a solution of di-tert-butyl (1S,2R,3S,4R,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-[(3,4-dichlorobenzyl)oxy]-4-[(methylsulfonyl)oxy]bicyclo[3.1.0]hexane-2,6-dicarboxylate (0.80 g, 0.84 mmol) in dimethylformamide (1.68 mL. After heating for 2 days at 80° C., pour the solution into brine and extract with ethyl acetate three times, dry the combined organic phases with sodium sulfate, filter and concentrate under reduced pressure. Purify by flash chromatography eluting with 10% ethyl acetate/CH2Cl2 to yield the title compound as an oil (0.576 g, 0.84 mmol, 100%). MS (m/z): 685/687/689 (M+1).

Workup

  1. extractionextract with ethyl acetate three times
  2. dry with materialdry the combined organic phases with sodium sulfate
  3. filtrationfilter
  4. concentrationconcentrate under reduced pressure
  5. customPurify by flash chromatography
  6. washeluting with 10% ethyl acetate/CH2Cl2

Sources & evidence

ORD record
ord-e7dcbeab7bf1470882595232f03fb5f6
Source dataset
uspto-grants-2015_06
Patent number
US09056844B2

Reaction notes

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