Diisopropylethylamine → 1-[1-(4-Chloro-phenyl)-cyclobutanecarbonyl]-piperidin-3-ylmethyl alcohol

HRID 50646

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:20](O)=[O:21])[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:20]([N:1]3[CH2:6][CH2:5][CH2:4][CH:3]([CH2:7][OH:8])[CH2:2]3)=[O:21])[CH2:19][CH2:18][CH2:17]2)=[CH:14][CH:15]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 3-piperidinemethanol (5.0 g, 43.4 mmol), 1-(4-chlorophenyl)-1-cyclobutanecarboxylic acid (9.14 g, 43.4 mmol), and diisopropylethylamine (11.22 g, 86.8 mmol) in dichloromethane (100 mL) at 0° C. was added PyBroP® (22.26 g, 47.8 mmol). The reaction was stirred at 0° C. for 1 h and then at room temperature for 4 h. The reaction mixture was washed successively with water, 1 N HCl, water, sat. sodium bicarbonate solution, and water (100 mL each). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated by rotary evaporation. The residue was purified by chromatography on silica gel, eluting with dichloromethane/methanol (96:4) to give 5.8 g of the amide 1 as a thick gum.

Workup

waitat room temperature for 4 h
washThe reaction mixture was washed successively with water, 1 N HCl, water, sat. sodium bicarbonate solution, and water (100 mL each)
dry with materialThe organic layer was dried over anhydrous sodium sulfate
filtrationfiltered
concentrationconcentrated by rotary evaporation
customThe residue was purified by chromatography on silica gel
washeluting with dichloromethane/methanol (96:4)

Sources & evidence

ORD record: ord-6469e73dfeb34cdd8edaa7e1eb69d9b9
Source dataset: uspto-grants-2004_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06713479B2

Linked notes

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