Formic Acid → 4-(4-Acetamido-4-phenylpiperidino)-2-(3,4-dichlorophenyl)-N-formyl-N-[3,5-bis(trifluoromethyl)benzyl]butylamine

HRID 613789Notes

Reaction equation

HRID 613789 reaction equation
[CH:1]([OH:3])=O.Cl.CN(C)CCCN=C=NCC.[C:16]([NH:19][C:20]1([C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)[CH2:25][CH2:24][N:23]([CH:26]([CH2:39][C:40]2[CH:45]=[C:44]([C:46]([F:49])([F:48])[F:47])[CH:43]=[C:42]([C:50]([F:53])([F:52])[F:51])[CH:41]=2)[CH2:27][CH:28]([C:31]2[CH:36]=[CH:35][C:34]([Cl:37])=[C:33]([Cl:38])[CH:32]=2)[CH2:29][NH2:30])[CH2:22][CH2:21]1)(=[O:18])[CH3:17].CN1CCOCC1>ClCCl.Cl.O>[C:16]([NH:19][C:20]1([C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)[CH2:21][CH2:22][N:23]([CH:26]([CH2:39][C:40]2[CH:41]=[C:42]([C:50]([F:51])([F:53])[F:52])[CH:43]=[C:44]([C:46]([F:47])([F:48])[F:49])[CH:45]=2)[CH2:27][CH:28]([C:31]2[CH:36]=[CH:35][C:34]([Cl:37])=[C:33]([Cl:38])[CH:32]=2)[CH2:29][NH:30][CH:1]=[O:3])[CH2:24][CH2:25]1)(=[O:18])[CH3:17]

Participants

8

Reactant 4

HCID 284Formic AcidHCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 570149314-(4-Acetamido-4-phenylpiperidino)-2-(3,4-dichlorophenyl)-N-[3,5-bis(trifluoromethyl)benzyl]butylamine

Product 1

HCID 867523394-(4-Acetamido-4-phenylpiperidino)-2-(3,4-dichlorophenyl)-N-formyl-N-[3,5-bis(trifluoromethyl)benzyl]butylamine

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Procedure

To a 0° C. solution of formic acid (0.09 mL) in dichloromethane (3 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.23 g) and the mixture stirred for 15 minutes. To this mixture was added a solution of 4-(4-acetamido-4-phenylpiperidino)-2-(3,4-dichlorophenyl)-N-[3,5-bis(trifluoromethyl)benzyl]butyl amine (0.40) and N-methylmorpholine (0.13 mL) in dichloromethane (5 mL). The mixture was allowed to warm to room temperature overnight, and was diluted with 1N hydrochloric acid (5 mL), dichloromethane, and water (5 mL). The layers were separated and the the aqueous phase was extracted with dichloromethane (10 mL). The combined organic layers were washed (brine), dried, and evaporated to afford material which was purified by chromatography with dichloromethane:methanol (20:1) as eluent, to give a hydrate of the title compound (0.206 g); mp 108-110° C.; NMR: 8.1-7.5 (m,6), 7.3 (m,6), 4.75-4.40 (m,2), 3.75-3.3 (m,4), 3.3-3.0 (m,4), 2.85 (m,1), 1.95 (s,3), 2.25-1.80 (m,4); MS: m/z=688(M+l,100%); TLC: Rf=0.46 (10:1 dichloromethane:methanol). Analysis for C33H33C2F6N3O2.1.50 H2O: Calculated: C, 55.39; H, 5.07; N, 5.87; Found: C, 55.38; H, 4.77; N, 5.84.

Workup

  1. customThe layers were separated
  2. extractionthe the aqueous phase was extracted with dichloromethane (10 mL)
  3. washThe combined organic layers were washed (brine)
  4. customdried
  5. customevaporated
  6. customto afford material which
  7. customwas purified by chromatography with dichloromethane:methanol (20:1) as eluent

Sources & evidence

ORD record
ord-af7a25b38e2a44be999f2c26fadad0b1
Source dataset
uspto-grants-1999_12
Patent number
US06008223

Reaction notes

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