4-Methylmorpholine → 4-{(R)-3-[3,5-Dichloro-4'-(4-trifluoromethyl-piperidine-1-carbonyl)-biphenyl-4-ylmethyl]-2-oxo-pyrrolidin-1-yl}-piperidine-1-carboxylic acid tert-butyl ester

HRID 1171155Notes

Reaction equation

HRID 1171155 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH2:18][CH2:17][C@@H:16]([CH2:19][C:20]3[C:25]([Cl:26])=[CH:24][C:23]([C:27]4[CH:32]=[CH:31][C:30]([C:33](O)=[O:34])=[CH:29][CH:28]=4)=[CH:22][C:21]=3[Cl:36])[C:15]2=[O:37])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[F:39][C:40]([F:48])([F:47])[CH:41]1[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]1.CCN=C=NCCCN(C)C.Cl.ON1C2C=CC=CC=2N=N1.CN1CCOCC1>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([N:14]2[CH2:18][CH2:17][C@@H:16]([CH2:19][C:20]3[C:25]([Cl:26])=[CH:24][C:23]([C:27]4[CH:28]=[CH:29][C:30]([C:33]([N:44]5[CH2:45][CH2:46][CH:41]([C:40]([F:48])([F:47])[F:39])[CH2:42][CH2:43]5)=[O:34])=[CH:31][CH:32]=4)=[CH:22][C:21]=3[Cl:36])[C:15]2=[O:37])[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 162181604-(Trifluoromethyl)piperidine hydrochlorideHCID 666716484-[(R)-3-(4'-Carboxy-3,5-dichloro-biphenyl-4-ylmethyl)-2-oxo-pyrrolidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 666716564-{(R)-3-[3,5-Dichloro-4'-(4-trifluoromethyl-piperidine-1-carbonyl)-biphenyl-4-ylmethyl]-2-oxo-pyrrolidin-1-yl}-piperidine-1-carboxylic acid tert-butyl esterYield 81.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Stir a solution of 4-[(R)-3-(4′-Carboxy-3,5-dichloro-biphenyl-4-ylmethyl)-2-oxo-pyrrolidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (Preparation 25) (0.1 g, 0.18 mmol), 4-(Trifluoromethyl)piperidine Hydrochloride (42 mg, 0.22 mmol), N-(3-Dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (42 mg, 0.22 mmol), 1-Hydroxybenzotriazole (73 mg, 0.22 mmol) and 4-Methylmorpholine (0.08 mL, 0.73 mmol) in CH2Cl2 (3 mL) at room temperature for 6 hr. Quench the reaction with 1N HCl and extract with EtOAc. Wash the organic with brine, dry over MgSO4, and filter. Purify the crude by silica gel column chromatography using Hexanes:EtOAc to elute the pure product. Remove the solvent to afford 0.10 g (80%) of desired product. MS (m/e): 582 (M−BOC+).

Workup

  1. customQuench
  2. customthe reaction with 1N HCl
  3. extractionextract with EtOAc
  4. washWash the organic with brine
  5. dry with materialdry over MgSO4
  6. filtrationfilter
  7. customPurify the crude by silica gel column chromatography
  8. washEtOAc to elute the pure product
  9. customRemove the solvent

Sources & evidence

ORD record
ord-5f611d6420c14c4a84b853708d9d8bce
Source dataset
uspto-grants-2010_11
Patent number
US07829582B2

Reaction notes

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