Hydrochloric Acid → tert-Butyl (S)-1-(5-(3-fluoro-4-nitrophenyl)-1,3,4-thiadiazol-2-yl-boc-amino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate

HRID 2075311Notes

Reaction equation

HRID 2075311 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:11]2[S:15][C:14]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[N:13][N:12]=2)[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9].C(=O)([O-])[O-].[Cs+].[Cs+].[F:30][C:31]([F:54])([F:53])[C:32]1[CH:52]=[CH:51][C:35]([CH2:36][C@H:37]2[CH2:41]OS(=O)(=O)[N:38]2[C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])=[CH:34][CH:33]=1.Cl>C1COCC1.CCOC(C)=O>[F:1][C:2]1[CH:3]=[C:4]([C:11]2[S:15][C:14]([N:16]([C:17]([O:18][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:23])[CH2:41][C@@H:37]([NH:38][C:44](=[O:45])[O:46][C:47]([CH3:50])([CH3:49])[CH3:48])[CH2:36][C:35]3[CH:51]=[CH:52][C:32]([C:31]([F:54])([F:53])[F:30])=[CH:33][CH:34]=3)=[N:13][N:12]=2)[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 57634052tert-Butyl (4S)-4-(4-(trifluoromethyl)benzyl)-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxideHCID 57991903tert-Butyl 5-(3-fluoro-4-nitrophenyl)-1,3,4-thiadiazol-2-ylcarbamate

Product 1

HCID 57991896tert-Butyl (S)-1-(5-(3-fluoro-4-nitrophenyl)-1,3,4-thiadiazol-2-yl-boc-amino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

tert-Butyl 5-(3-fluoro-4-nitrophenyl)-1,3,4-thiadiazol-2-ylcarbamate (0.587 g, 1.72 mmol) and cesium carbonate (1.12 g, 3.45 mmol) were heated to 50° C. in 15 mL THF in a round bottle flask. (S)-tert-Butyl 4-(4-(trifluoromethyl)benzyl)-1,2,3-oxathiazolidine-3-carboxylate-2,2-dioxide (0.855 g, 2.24 mmol) in 10 mL THF was added to the flask dropwise, and the mixture was heated at 50° C. for 30 minutes. The flask was then cooled to 20° C., and 10 mL 1 N HCl was added to the flask. The resulting mixture was stirred at room temperature for 30 minutes. The reaction mixture was combined with 200 mL EtOAc. The organic phase was washed with water, twice with saturated ammonium sulfate, and dried over sodium sulfate. After removing the solvent, the product was obtained as yellow oil. LCMS indicated two major peaks with the same desired product M+1. The product thus obtained was used directly in the next step.

Workup

  1. temperatureThe flask was then cooled to 20° C.
  2. washThe organic phase was washed with water, twice with saturated ammonium sulfate
  3. dry with materialdried over sodium sulfate
  4. customAfter removing the solvent
  5. customthe product was obtained as yellow oil
  6. customThe product thus obtained

Sources & evidence

ORD record
ord-7d987e4518604691827e3c6f7bd1fc4e
Source dataset
uspto-grants-2011_04
Patent number
US07919504B2

Reaction notes

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