Triethylamine → HCID 86757778, compound

HRID 1699470Notes

Reaction equation

HRID 1699470 reaction equation
[F:1][C:2]([F:34])([F:33])[C:3]1[CH:4]=[C:5]([CH:26]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:28]=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]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=1)=[O:7].Cl.[C:36]1([C:42]2([C:48]([N:50]3[CH2:54][CH2:53][CH2:52][CH2:51]3)=[O:49])[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]2)[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.C(N(CC)CC)C.C([BH3-])#N.[Na+]>C1COCC1.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].C(O)C>[F:32][C:29]([F:30])([F:31])[C:27]1[CH:26]=[C:5]([CH:4]=[C:3]([C:2]([F:33])([F:34])[F:1])[CH:28]=1)[C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([N:45]2[CH2:46][CH2:47][C:42]([C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=3)([C:48]([N:50]3[CH2:54][CH2:53][CH2:52][CH2:51]3)=[O:49])[CH2:43][CH2:44]2)[CH2:10][C@@H:9]1[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]([F:23])([F:24])[F:25])=[CH:18][CH:17]=1)=[O:7].[F:32][C:29]([F:30])([F:31])[C:27]1[CH:26]=[C:5]([CH:4]=[C:3]([C:2]([F:33])([F:34])[F:1])[CH:28]=1)[C:6]([N:8]1[CH2:13][CH2:12][C@@H:11]([N:45]2[CH2:46][CH2:47][C:42]([C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=3)([C:48]([N:50]3[CH2:54][CH2:53][CH2:52][CH2:51]3)=[O:49])[CH2:43][CH2:44]2)[CH2:10][C@@H:9]1[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]([F:23])([F:24])[F:25])=[CH:18][CH:17]=1)=[O:7]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 30194841-((4-Phenyl-4-piperidyl)carbonyl)pyrrolidine monohydrochlorideHCID 5003444Sodium cyanoborohydrideHCID 18319935HCID 18319935, compound

Product 2

HCID 86757778HCID 86757778, compoundYield 55%HCID 86757779HCID 86757779, compoundYield 18%

Reagents, catalysts & solvents 3

HCID 702EthanolSolvent2×HCID 8028TetrahydrofuranSolventHCID 11026Titanium isopropoxideSolvent

Procedure

A solution of intermediate 15 (0.01 mol), 1-(4-phenyl-4-piperidinylcarbonyl)pyrrolidine hydrochloride (0.01 mol) and triethylamine (0.015 mol) in THF (10 ml) and titanium(IV)isopropoxide (3.72 ml) was stirred at RT for 4 hours. Ethanol (10 ml) and sodium cyanoborohydride (0.01 mol) were added. The mixture was stirred for a few hours. Ice and ethanol (10 ml) were added and the mixture was stirred at RT for 30 minutes and then filtered over decalite. The solvent was evaporated and the residue extracted with CH2Cl2. The organic layer was separated, dried, filtered and the solvent was evaporated. The residue was purified by HPLC over silica gel (eluent: CH2Cl2/CH3OH 95/5). Two pure fractions were collected and their solvents were evaporated. The residue was crystallized from DIPE. The precipitate was filtered off and dried, yielding 4.07 g of (±)-cis-1-[3,5-bis(trifluoromethyl)-benzoyl]-4-[4-phenyl-4-(1-pyrrolidinylcarbonyl)-1-piperidinyl]-2-[[4-(trifluoromethyl)-phenyl]methyl]piperidine (55%) (compound 111) and 1.3 g of (±)-trans-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[4-phenyl-4-(1-pyrrolidinylcarbonyl)-1-piperidinyl]-2-[[4-(trifluoromethyl)phenyl]methyl]-piperidine (18%) (compound 112).

Workup

  1. stirringthe mixture was stirred at RT for 30 minutes
  2. filtrationfiltered over decalite
  3. customThe solvent was evaporated
  4. extractionthe residue extracted with CH2Cl2
  5. customThe organic layer was separated
  6. customdried
  7. filtrationfiltered
  8. customthe solvent was evaporated
  9. customThe residue was purified by HPLC over silica gel (eluent: CH2Cl2/CH3OH 95/5)
  10. customTwo pure fractions were collected
  11. customtheir solvents were evaporated
  12. customThe residue was crystallized from DIPE
  13. filtrationThe precipitate was filtered off
  14. customdried

Sources & evidence

ORD record
ord-aa12945ae7924757b7b47d9265c472dd
Source dataset
uspto-grants-2002_02
Patent number
US06346540B1

Reaction notes

Loading…