Diisopropylethylamine → [1-(4-Chloro-phenyl)-cyclopentyl]-(3-hydroxymethyl-piperidin-1-yl)-methanone

HRID 1788080Notes

Reaction equation

HRID 1788080 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][CH:3]([CH2:7][OH:8])[CH2:2]1.[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2([C:21](O)=[O:22])[CH2:20][CH2:19][CH2:18][CH2:17]2)=[CH:12][CH:11]=1.C(N(C(C)C)CC)(C)C.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>ClCCl>[Cl:9][C:10]1[CH:11]=[CH:12][C:13]([C:16]2([C:21]([N:1]3[CH2:6][CH2:5][CH2:4][CH:3]([CH2:7][OH:8])[CH2:2]3)=[O:22])[CH2:20][CH2:19][CH2:18][CH2:17]2)=[CH:14][CH:15]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 974471-(4-Chlorophenyl)cyclopentanecarboxylic acidHCID 107308Piperidin-3-ylmethanolHCID 2733179PyBroP

Product 1

HCID 22335026[1-(4-Chloro-phenyl)-cyclopentyl]-(3-hydroxymethyl-piperidin-1-yl)-methanoneYield 156.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of piperdin-3-yl methanol (0.342 g, 2.97 mmol), 1-(4-chloro-phenyl)-cyclopentylcarboxylic acid (1.0 g, 4.45 mmol), diisopropylethyl amine (1.9, 15.00 mmol) in dichloromethane (7 mL) was stirred at room temperature. PyBroP (2.07 g, 4.45 mmol) 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 (95:5 hexane:ethyl acetate) to yield the desired compound (1.50 g). C18H24ClNO2, LRMS (m/z)=322 (MH+).

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-3d2ddcff4e1c4aee8e997e55b2747644
Source dataset
uspto-grants-2009_03
Patent number
US07511141B2

Reaction notes

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