Cesium carbonate → 1,1-Dimethylethyl (2-bromo-1,3-thiazol-5-yl)((2S)-2-((((1,1-dimethylethyl)oxy)carbonyl)amino)-3-(4-(trifluoromethyl)phenyl)propyl)-carbamate

HRID 598873Notes

Reaction equation

HRID 598873 reaction equation
[Br:1][C:2]1[S:3][C:4]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[CH:5][N:6]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[F:21][C:22]([F:45])([F:44])[C:23]1[CH:28]=[CH:27][C:26]([CH2:29][CH:30]2[CH2:34]OS(=O)(=O)[N:31]2[C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])=[CH:25][CH:24]=1>CN(C=O)C.CCOCC>[Br:1][C:2]1[S:3][C:4]([N:7]([CH2:34][C@@H:30]([NH:31][C:37]([O:39][C:40]([CH3:41])([CH3:43])[CH3:42])=[O:38])[CH2:29][C:26]2[CH:25]=[CH:24][C:23]([C:22]([F:21])([F:44])[F:45])=[CH:28][CH:27]=2)[C:8](=[O:14])[O:9][C:10]([CH3:11])([CH3:13])[CH3:12])=[CH:5][N:6]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 46911876tert-butyl N-(2-bromo-1,3-thiazol-5-yl)carbamateHCID 57950494HCID 57950494, compound

Product 1

HCID 579506051,1-Dimethylethyl (2-bromo-1,3-thiazol-5-yl)((2S)-2-((((1,1-dimethylethyl)oxy)carbonyl)amino)-3-(4-(trifluoromethyl)phenyl)propyl)-carbamateYield 91%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
50 °C

Procedure

To a 250 mL round-bottomed flask was added tert-butyl 2-bromothiazol-5-ylcarbamate (0.75 g, 2.69 mmol), DMF (26.9 mL, 2.69 mmol), and cesium carbonate (1.75 g, 5.37 mmol). The mixture was warmed to 50° C. and 1,1-dimethylethyl 4-((4-(trifluoromethyl)phenyl)methyl)-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide (1.13 g, 2.96 mmol, Scheme 1) was added slowly in 10 mL DMF. After 1 hour, the mixture was cooled, diluted with ether (100 mL) and washed with brine (3×50 mL). The organic layer was dried over sodium sulfate, evaporated onto a plug of silica gel and purified by chromatography through a Redi-Sep® pre-packed silica gel column (40 g), eluting with a gradient of 20% to 100% EtOAc in hexane, to provide the product (1.42 g, 91% yield) as a white amorphous solid. LCMS (API-ES) m/z (%): 582 (100%, M+H).

Workup

  1. temperaturethe mixture was cooled
  2. washwashed with brine (3×50 mL)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. customevaporated onto a plug of silica gel
  5. custompurified by chromatography through a Redi-Sep® pre-packed silica gel column (40 g)
  6. washeluting with a gradient of 20% to 100% EtOAc in hexane

Sources & evidence

ORD record
ord-e213f4bacb8e41cda937c2167e60d37e
Source dataset
uspto-grants-2011_03
Patent number
US07897619B2

Reaction notes

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