Water → HCID 86684917, compound

HRID 2402912Notes

Reaction equation

HRID 2402912 reaction equation
[C:1]([C:3]1([NH:6][C:7]([C@H:9]2[N:13]([C:14]([C:16]3([C:19]([F:22])([F:21])[F:20])[CH2:18][CH2:17]3)=[O:15])[CH2:12][C@@H:11](OS(C3C=CC=CC=3)(=O)=O)[CH2:10]2)=[O:8])[CH2:5][CH2:4]1)#[N:2].C(=O)([O-])[O-].[K+].[K+].[Cl:39][C:40]1[CH:45]=[C:44]([O:46][C@@H:47]([CH3:52])[C:48]([F:51])([F:50])[F:49])[CH:43]=[CH:42][C:41]=1[SH:53].O>CC(N(C)C)=O.O1CCCC1>[C:1]([C:3]1([NH:6][C:7]([C@@H:9]2[CH2:10][C@@H:11]([S:53][C:41]3[CH:42]=[CH:43][C:44]([O:46][C@@H:47]([CH3:52])[C:48]([F:49])([F:50])[F:51])=[CH:45][C:40]=3[Cl:39])[CH2:12][N:13]2[C:14]([C:16]2([C:19]([F:20])([F:22])[F:21])[CH2:18][CH2:17]2)=[O:15])=[O:8])[CH2:4][CH2:5]1)#[N:2]

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 86684906HCID 86684906, compoundHCID 86684916HCID 86684916, compound

Product 1

HCID 86684917HCID 86684917, compoundYield 110.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent

Procedure

Benzenesulfonic acid (3S,5S)-5-(1-cyano-cyclopropylcarbamoyl)-1-(1-trifluoromethyl-cyclopropanecarbonyl)-pyrrolidin-3-yl ester (225 g, 477 mmol) was dissolved in dimethylacetamide (1.125 L) and potassium carbonate (166.5 g, 1.193 mol) was added. At room temperature, a solution of 2-chloro-4-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-benzenethiol (142 g, 553.2 mmol) in tetrahydrofuran (135 mL) was added slowly, keeping the internal temperature below 29° C. (ice bath cooling necessary). The mixture was stirred for 5.5 h at room temperature. After addition of ice (700 g) and water (2 L), the mixture was extracted with tert-butyl-methylether (1×1.5 L, 3×750 mL). The combined organic extracts were washed with brine (450 mL) and concentrated in vacuo to yield the title compound as a brown viscous oil (300.4 g). The crude product (containing dimethylacetamide) was used in the next step without further purification.

Workup

  1. temperaturethe internal temperature below 29° C. (ice bath cooling necessary)
  2. extractionthe mixture was extracted with tert-butyl-methylether (1×1.5 L, 3×750 mL)
  3. washThe combined organic extracts were washed with brine (450 mL)
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ee24ee77b7414d65912d8739c5d34f17
Source dataset
uspto-grants-2014_08
Patent number
US08796471B2

Reaction notes

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