Isopropyl Acetate → (2S,4R)-4-(2-Trifluoromethyl-benzenesulfonyl)-1-(5-trifluoromethyl-[1,3,4]thiadiazol-2-yl)-pyrrolidine-2-carboxylic Acid (1-cyano-cyclopropyl)-amide

HRID 1697608Notes

Reaction equation

HRID 1697608 reaction equation
[F-].[K+].C[O:4][C:5]([C@@H:7]1[CH2:11][C@@H:10]([S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[C:21]([F:24])([F:23])[F:22])(=[O:14])=[O:13])[CH2:9][N:8]1[C:25]1[S:26][C:27]([C:30]([F:33])([F:32])[F:31])=[N:28][N:29]=1)=O.C([N:36](CC)CC)C.COC([C@@H:45]1[CH2:49][C@@H:48](S(C2C=CC=CC=2C(F)(F)F)(=O)=O)[CH2:47][NH:46]1)=O.C(OC([C@@H]1C[C@H](S(C2C=CC=CC=2C(F)(F)F)(=O)=O)CN1)=O)C.ClC1SC(C(F)(F)F)=NN=1.C(OC(C)=O)(C)C>CN(C)C(=O)C>[C:47]([C:48]1([NH:36][C:5]([C@@H:7]2[CH2:11][C@@H:10]([S:12]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[C:21]([F:22])([F:23])[F:24])(=[O:13])=[O:14])[CH2:9][N:8]2[C:25]2[S:26][C:27]([C:30]([F:32])([F:33])[F:31])=[N:28][N:29]=2)=[O:4])[CH2:45][CH2:49]1)#[N:46]

Participants

8

Reactant 6

HCID 7915Isopropyl AcetateHCID 8471TriethylamineHCID 132467892-Chloro-5-trifluoromethyl-(1,3,4)thiadiazoleHCID 66770899(2S,4S)-4-(2-trifluoromethyl-benzenesulfonyl)-pyrrolidine-2-carboxylic acid ethyl esterHCID 66771131(2S,4R)-4-(2-trifluoromethyl-benzenesulfonyl)-pyrrolidine-2-carboxylic acid methyl esterHCID 86646845(2S,4R)-4-(2-Trifluoromethyl-benzenesulfonyl)-1-(5-trifluoromethyl-[1,3,4]thiadiazol-2-yl)-pyrrolidine-2-carboxylic acid methyl ester Potassium fluoride

Product 1

HCID 59543797(2S,4R)-4-(2-Trifluoromethyl-benzenesulfonyl)-1-(5-trifluoromethyl-[1,3,4]thiadiazol-2-yl)-pyrrolidine-2-carboxylic Acid (1-cyano-cyclopropyl)-amideYield 69%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

(2S,4R)-4-(2-Trifluoromethyl-benzenesulfonyl)-1-(5-trifluoromethyl-[1,3,4]thiadiazol-2-yl)-pyrrolidine-2-carboxylic acid methyl ester Potassium fluoride (26 mg, 445 umol) and triethylamine (62 ul, 445 umol) were added to a solution of (2S,4R)-4-(2-trifluoromethyl-benzenesulfonyl)-pyrrolidine-2-carboxylic acid methyl ester (50 mg, 148 umol; prepared as described for the corresponding (2S,4S)-4-(2-trifluoromethyl-benzenesulfonyl)-pyrrolidine-2-carboxylic acid ethyl ester in example 192e) and 2-chloro-5-trifluoromethyl-[1,3,4]thiadiazole (31 mg, 163 umol; CAS Reg. No. 53645-98-0) in N,N-dimethylacetamide (1 ml). The reaction mixture was heated in a microwave oven to 120° C. for 90 min. Ice water/0.1 N aqueous HCl solution 1/1 and iPrOAc were added and the layers were separated. The aqueous layer was extracted one more time with iPrOAc, the combined organic layers were washed with ice water/brine 1/1 and dried over Na2SO4. The solvent was removed under reduced pressure to give the title compound as yellow solid (50 mg, 102 umol; 69%) which was sufficiently pure to be used in the next reaction step. MS (ESI): m/z=558.2 [M+H]+.

Workup

  1. customprepared
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted one more time with iPrOAc
  4. washthe combined organic layers were washed with ice water/brine 1/1
  5. dry with materialdried over Na2SO4
  6. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-bcb980d3934048a7b14c8260d86a30d6
Source dataset
uspto-grants-2012_04
Patent number
US08163793B2

Reaction notes

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