Water → HCID 86585231, compound

HRID 2186722Notes

Reaction equation

HRID 2186722 reaction equation
[F:1][C:2]([F:32])([F:31])[C:3]1[CH:4]=[C:5]([CH:24]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:26]=1)[C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][C@H:9]1[CH2:14][C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[NH:17][CH:16]=1)=[O:7].O.[C:34]([O-:37])([O-])=[O:35].[K+].[K+]>C1COCC1.CC(OC)(C)C>[F:30][C:27]([F:28])([F:29])[C:25]1[CH:24]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:31])[F:32])[CH:26]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:34]([O:37][C:3]([CH3:4])([CH3:26])[CH3:2])=[O:35])[CH2:10][C@H:9]1[CH2:14][C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[NH:17][CH:16]=1)=[O:7]

Participants

6

Reactant 3

HCID 962WaterHCID 11430Potassium CarbonateHCID 10972505(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-ylmethyl)piperazine

Product 1

HCID 86585231HCID 86585231, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 15413tert-Butyl methyl etherSolvent

Procedure

First 50 ml of a 55% by weight solution of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-ylmethyl)-piperazine in THF and then 25 ml water were added to a suspension of 7.4 9 K2CO3 in 150 ml THF. A solution of 12.2 g tert. butoxycarbonyl anhydride in 50 ml THF was added to this receiving solution, and the mixture was stirred for 12 hours at room temperature. After reduction of the reaction mixture in a vacuum, the residue was taken up in 300 ml MTBE, and the organic phase was washed, in succession, twice with 100 ml portions of water, once with 50 ml of a 15% by weight aqueous tartaric acid solution and another four times with 100 ml portions of water, and then dried over sodium sulfate/SiO2. After filtering out the drying agent, the filtrate was reduced in a vacuum, and the residue was taken up in 20 ml MTBE. After heating to 60° C., 120 ml ligroin was added, and the volume was then reduced by approximately 100 ml by vacuum distillation. After another addition of 100 ml ligroin, the mixture was left to stand for 3 days to precipitate. The precipitated solid was filtered out, washed three times more with 30 ml portions of ligroin and dried at 60° C. in a vacuum. 82.0 g of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-ylmethyl]-4-(tert.butoxycarbonyl)piperazine were obtained as a solid, melting point 155-156° C.

Workup

  1. washthe organic phase was washed, in succession, twice with 100 ml portions of water, once with 50 ml of a 15% by weight aqueous tartaric acid solution
  2. dry with materialanother four times with 100 ml portions of water, and then dried over sodium sulfate/SiO2
  3. filtrationAfter filtering out the drying agent
  4. temperatureAfter heating to 60° C.
  5. addition120 ml ligroin was added
  6. distillationthe volume was then reduced by approximately 100 ml by vacuum distillation
  7. additionAfter another addition of 100 ml ligroin
  8. waitthe mixture was left
  9. waitto stand for 3 days
  10. customto precipitate
  11. filtrationThe precipitated solid was filtered out
  12. washwashed three times more with 30 ml portions of ligroin
  13. customdried at 60° C. in a vacuum

Sources & evidence

ORD record
ord-5f926d5fca6a4a63bc43ba0dcbb4adac
Source dataset
uspto-grants-2002_06
Patent number
US06407106B1

Reaction notes

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