Potassium Carbonate → (+/-)-trans-1-[3,5-Bis(trifluoromethyl)benzoyl]-4-[4-(5,6,7,10-tetrahydro-7-methylimidazo[1,2-a]pyrrolo[3,2-d]azepin-10-ylidene)-1-piperidinyl]-2-(phenylmethyl)piperidine

HRID 1068661Notes

Reaction equation

HRID 1068661 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[F:15][C:16]([F:44])([F:43])[C:17]1[CH:18]=[C:19]([CH:36]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:38]=1)[C:20]([N:22]1[CH2:27][CH2:26][C:25](=O)[CH2:24][CH:23]1[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:21].[CH3:45][N:46]1[C:55]2[CH2:54][CH2:53][N:52]3[CH:56]=[CH:57][N:58]=[C:51]3[C:50](=[C:59]3[CH2:64][CH2:63][NH:62][CH2:61][CH2:60]3)[C:49]=2[CH:48]=[CH:47]1.C([O-])([O-])=O.[K+].[K+]>ClCCCl.O.C(O)(=O)C>[F:15][C:16]([F:44])([F:43])[C:17]1[CH:18]=[C:19]([CH:36]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:38]=1)[C:20]([N:22]1[CH2:27][CH2:26][C@@H:25]([N:62]2[CH2:63][CH2:64][C:59](=[C:50]3[C:49]4[CH:48]=[CH:47][N:46]([CH3:45])[C:55]=4[CH2:54][CH2:53][N:52]4[CH:56]=[CH:57][N:58]=[C:51]34)[CH2:60][CH2:61]2)[CH2:24][C@@H:23]1[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:21]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 11026356(+/-)-1-[3,5-Bis(trifluoromethyl)benzoyl]-2-(phenylmethyl)-4-piperidinoneHCID 112309711-Methyl-4-piperidin-4-ylidene-1,4,8,9-tetrahydro-1,5,7a-triaza-cyclopenta[f]azulene

Product 1

HCID 86757038(+/-)-trans-1-[3,5-Bis(trifluoromethyl)benzoyl]-4-[4-(5,6,7,10-tetrahydro-7-methylimidazo[1,2-a]pyrrolo[3,2-d]azepin-10-ylidene)-1-piperidinyl]-2-(phenylmethyl)piperidineYield 4%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

Sodium triacetoxyborohydride (8.5 g) and acetic acid (2.4 g) were added dropwise to a mixture of (±)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(phenylmethyl)-4-piperidinone (4.3 g) and 5,6,7,10-tetrahydro-7-methyl-10-(4-piperidinylidene)imidazo[1,2-a]pyrrolo[3,2-d]azepine (2.7 g) in 1,2-dichloroethane (100 ml) and the mixture was stirred at RT overnight. Water and K2CO3 (5 g) were added and the layers were separated. The aqueous layer was extracted with CH2Cl2. The combined organic layers were dried, filtered and the solvent evaporated. The residue was purified by HPLC over silica gel (eluent: CH2Cl2/CH3OH 96/4 to 85/15). The pure fractions were collected and evaporated, yielding 1.04 g (15%) of fraction 1 and 0.26 g (4%) of (±)-trans-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[4-(5,6,7,10-tetrahydro-7-methylimidazo[1,2-a]pyrrolo[3,2-d]azepin-10-ylidene)-1-piperidinyl]-2-(phenylmethyl)piperidine (comp. 2; mp. 141.5° C.). Fraction 1 was repurified by HPLC over NH2-Kromasil (eluent: 100% CH2Cl2). The pure fractions were collected and the solvent was evaporated, yielding 0.75 g (11%) of (±)-cis-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[4-(5,6,7,10-tetrahydro-7-methylimidazo[1,2-a]-pyrrolo[3,2-d]azepin-10-ylidene)-1-piperidinyl]-2-(phenylmethyl)piperidine (comp. 3; mp. 133.0° C.).

Workup

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted with CH2Cl2
  3. customThe combined organic layers were dried
  4. filtrationfiltered
  5. customthe solvent evaporated
  6. customThe residue was purified by HPLC over silica gel (eluent: CH2Cl2/CH3OH 96/4 to 85/15)
  7. customThe pure fractions were collected
  8. customevaporated

Sources & evidence

ORD record
ord-80329050d39c4a99afcb537ea024892f
Source dataset
uspto-grants-2001_06
Patent number
US06251894B1

Reaction notes

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