Ethanol → HCID 86619159, compound

HRID 1530930Notes

Reaction equation

HRID 1530930 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][C:11](=O)[CH2:10][CH:9]1[CH2:15][C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[C:18]([F:23])[CH:17]=1)=[O:7].[CH3:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([CH3:40])[C:35]=1[NH:41][C:42](=[O:50])[CH2:43][N:44]1[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]1.[BH4-].[Na+].C(O)C>CC(O)C.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].C(Cl)Cl.O>[F:31][C:2]([F:1])([F:32])[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][C@H:11]([N:47]2[CH2:48][CH2:49][N:44]([CH2:43][C:42]([NH:41][C:35]3[C:36]([CH3:40])=[CH:37][CH:38]=[CH:39][C:34]=3[CH3:33])=[O:50])[CH2:45][CH2:46]2)[CH2:10][C@@H:9]1[CH2:15][C:16]1[CH:17]=[C:18]([F:23])[CH:19]=[C:20]([F:22])[CH:21]=1)=[O:7]

Participants

9

Reactant 4

HCID 702EthanolHCID 2608606Cvt-2738HCID 4311764Sodium borohydrideHCID 18630845HCID 18630845, compound

Product 1

HCID 86619159HCID 86619159, compoundYield 8.2%

Reagents, catalysts & solvents 4

HCID 11026Titanium isopropoxideCatalystHCID 962WaterSolventHCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of (±)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-[(3,5-difluorophenyl)methyl]-4-piperidinone (0.0058 mol), N-(2,6-dimethylphenyl)-1-piperazineacetamide (0.0058 mol) and titanium(IV)isopropoxide (0.0064 mol) in 2-propanol (5 ml) was stirred at RT overnight. NaBH4 (0.0116 mol) and ethanol (15 ml) were added. The mixture was stirred for 2 day. Water (5 ml) was added and the mixture was stirred for 10 minutes. CH2Cl2 (200 ml) was added. The organic layer was separated, dried, filtered and the solvent was evaporated. This fraction was purified by HPLC over silica gel (eluent: CH2Cl2/CH3OH 98/2 to 90/10 over a 30-minute period). Two pure fractions (F1 and F2) were collected and their solvents were evaporated. F1 was purified by column chromatography over RP18 (eluent: NH4OAc (0.5% in H2O)/CH3CN 40/60). The pure fractions were collected and the solvent was evaporated. The residue was dried, yielding 0.33 g (8%) of (±)-cis-4-[1-[3,5-bis(trifluoromethyl)benzoyl]-2-[(3,5-difluorophenyl)methyl]-4-piperidinyl]-N-(2,6-dimethylphenyl)-1-piperazineacetamide (compound 132). F2 was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH 100/0 to 98/2 over a 30-minute period). The pure fractions were collected and the solvent was evaporated. The residue was dissolved in CH2Cl2, filtered and the solvent was evaporated. The residue was dried, yielding 0.24 g (6%) of (±)-trans-4-[1-[3,5-bis(trifluoromethyl)benzoyl]-2-[(3,5-difluorophenyl)methyl]-4-piperidinyl]-N-(2,6-dimethylphenyl)-1-piperazineacetamide (compound 133).

Workup

  1. stirringThe mixture was stirred for 2 day
  2. stirringthe mixture was stirred for 10 minutes
  3. customThe organic layer was separated
  4. customdried
  5. filtrationfiltered
  6. customthe solvent was evaporated
  7. customThis fraction was purified by HPLC over silica gel (eluent
  8. waitCH2Cl2/CH3OH 98/2 to 90/10 over a 30-minute period)
  9. customTwo pure fractions (F1 and F2) were collected
  10. customtheir solvents were evaporated
  11. customF1 was purified by column chromatography over RP18 (eluent: NH4OAc (0.5% in H2O)/CH3CN 40/60)
  12. customThe pure fractions were collected
  13. customthe solvent was evaporated
  14. customThe residue was dried

Sources & evidence

ORD record
ord-673a06c8801547c0ad8ace2ea93c682a
Source dataset
uspto-grants-2001_03
Patent number
US06197772B1

Reaction notes

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