Water → N-[(1S)-1-(4-{3-[2,6-bis(trifluoromethyl)pyridin-4-yl]-3-(trifluoromethyl)pyrrolidin-1-yl}phenyl)ethyl]cyclopropanecarboxamide

HRID 42633

Reaction equation

HRID 42633 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([NH:10][C:11]([CH:13]2[CH2:15][CH2:14]2)=[O:12])[CH3:9])=[CH:4][CH:3]=1.[F:16][C:17]([F:38])([F:37])[C:18]1[CH:23]=[C:22]([C:24]2([C:29]([F:32])([F:31])[F:30])[CH2:28][CH2:27][NH:26][CH2:25]2)[CH:21]=[C:20]([C:33]([F:36])([F:35])[F:34])[N:19]=1.CC(C)([O-])C.[Na+].O>C1(C)C=CC=CC=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[F:38][C:17]([F:16])([F:37])[C:18]1[CH:23]=[C:22]([C:24]2([C:29]([F:30])([F:31])[F:32])[CH2:28][CH2:27][N:26]([C:2]3[CH:7]=[CH:6][C:5]([C@@H:8]([NH:10][C:11]([CH:13]4[CH2:15][CH2:14]4)=[O:12])[CH3:9])=[CH:4][CH:3]=3)[CH2:25]2)[CH:21]=[C:20]([C:33]([F:34])([F:35])[F:36])[N:19]=1

Participants

7

Reactant 4

HCID 962WaterHCID 800360N-[(1S)-1-(4-bromophenyl)ethyl]cyclopropanecarboxamideHCID 23676156Sodium t-butoxideHCID 532621872,6-Bis(trifluoromethyl)-4-[3-(trifluoromethyl)pyrrolidin-3-yl]pyridine

Product 1

HCID 53261994N-[(1S)-1-(4-{3-[2,6-bis(trifluoromethyl)pyridin-4-yl]-3-(trifluoromethyl)pyrrolidin-1-yl}phenyl)ethyl]cyclopropanecarboxamideYield 100.9%

Reagents, catalysts & solvents 2

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 1140TolueneSolvent

Procedure

To the solution of N-[(1S)-1-(4-bromophenyl)ethyl]cyclopropanecarboxamide (0.134 g) and 2,6-bis(trifluoromethyl)-4-[3-(trifluoromethyl)pyrrolidin-3-yl]pyridine (0.195 g) in toluene was added sodium tert-butoxide (0.096 g), tris(dibenzylideneacetone)dipalladium chloroform complex (0.010 g) and xantphos (0.017 g) and the vessel was applied by Ar gas. The vessel was sealed and applied to microwave reactor at 120° C. for 10 min. The mixture was cooled to room temperature and then poured into water, which was then extracted twice with ethyl acetate. The organic layer was combined, which was then washed with water and dried over anhydrous magnesium sulfate. After the drying agent was filtered off, the solvent was distilled away under the reduced pressure, and the residue was then purified by silica gel chromatography to yield N-[(1S)-1-(4-{3-[2,6-bis(trifluoromethyl)pyridin-4-yl]-3-(trifluoromethyl)pyrrolidin-1-yl}phenyl)ethyl]cyclopropanecarboxamide (0.272 g).

Workup

  1. customThe vessel was sealed
  2. customat 120° C.
  3. customfor 10 min
  4. extractionwas then extracted twice with ethyl acetate
  5. washwhich was then washed with water
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationAfter the drying agent was filtered off
  8. distillationthe solvent was distilled away under the reduced pressure
  9. customthe residue was then purified by silica gel chromatography

Sources & evidence

ORD record
ord-8c9ab98ad9934ccd8557d2e19c071ef0
Source dataset
uspto-grants-2013_09
Patent number
US08536201B2

Linked notes

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