Diisopropylethylamine → 1-[1-(4-Chloro-phenyl)-cyclopropanecarbonyl]-piperidine-3-carboxylic acid ethyl ester

HRID 1788082Notes

Reaction equation

HRID 1788082 reaction equation
[CH2:1]([O:3][C:4]([CH:6]1[CH2:11][CH2:10][CH2:9][NH:8][CH2:7]1)=[O:5])[CH3:2].[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2([C:22](O)=[O:23])[CH2:21][CH2:20]2)=[CH:15][CH:14]=1.C(N(C(C)C)CC)(C)C.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>ClCCl>[CH2:1]([O:3][C:4]([CH:6]1[CH2:11][CH2:10][CH2:9][N:8]([C:22]([C:19]2([C:16]3[CH:15]=[CH:14][C:13]([Cl:12])=[CH:18][CH:17]=3)[CH2:21][CH2:20]2)=[O:23])[CH2:7]1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 986061-(p-Chlorophenyl)cyclopropanecarboxylic acidHCID 98969Ethyl nipecotateHCID 2733179PyBroP

Product 1

HCID 213032001-[1-(4-Chloro-phenyl)-cyclopropanecarbonyl]-piperidine-3-carboxylic acid ethyl esterYield 167.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of piperidine-3-carboxylic acid ethyl ester (10.0 g, 0.032 mol), 1-(4-chloro-phenyl)-cyclopropylcarboxylic acid (9.57 g, 0.049 mol), diisopropylethyl amine (21.0 g, 0.16 mol) in dichloromethane (160 mL) was stirred at room temperature. PyBroP (22.6 g, 0.49 mol) was added and the reaction mixture continued stirring at room temperature. After 12 h the reaction mixture was quenched with 10% KOH. The aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated to yield a crude oil. The crude material was purified using silica gel chromatography (80:20 hexane:ethyl acetate) to yield the amide (18.0 g).

Workup

  1. customAfter 12 h the reaction mixture was quenched with 10% KOH
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. concentrationconcentrated
  5. customto yield a crude oil
  6. customThe crude material was purified

Sources & evidence

ORD record
ord-126bbfff893842e280cfbd2c99e113f0
Source dataset
uspto-grants-2009_03
Patent number
US07511141B2

Reaction notes

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