Hydrochloric Acid → Ethyl 4-(4-aminophenyl)-4-methylpiperidine-1-carboxylate

HRID 2044105Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH3:19])[CH2:13][CH2:12][N:11]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[Li+].C[Si]([N-:25][Si](C)(C)C)(C)C.C1COCC1.Cl.[OH-].[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C2C=CC=CC=2)C=CC=CC=1P(C1CCCCC1)C1CCCCC1>[NH2:25][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH3:19])[CH2:13][CH2:12][N:11]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 65 °C

Procedure

A mixture of ethyl 4-(4-bromophenyl)-4-methylpiperidine-1-carboxylate (2.0 g, 6.13 mmol), biphenyl-2-yldicyclohexylphosphine (0.054 g, 0.153 mmol), 1M LiHMDS in THF (12.26 ml, 12.26 mmol), and Pd2(dba)3 (0.056 g, 0.061 mmol) was heated in a sealed vial at 65° C. overnight. The mixture was cooled to room temperature and treated with 1N aq. HCl (30.7 mL, 30.7 mmol) and stirred for 5 min. The mixture made basic with 1N NaOH and extracted twice with methylene chloride. The combined organic extracts were concentrated and the residue was purified by MPLC (ISCO, hexane/ethyl acetate, 24+40 g stacked silica gel columns) to give 924 mg (57%) of product as a yellow oil.

Workup

temperatureThe mixture was cooled to room temperature
extractionextracted twice with methylene chloride
concentrationThe combined organic extracts were concentrated
customthe residue was purified by MPLC (ISCO, hexane/ethyl acetate, 24+40 g stacked silica gel columns)

Sources & evidence

ORD record: ord-9b753626c19247bdb8e581ebbc813e03
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08586751B2

Reaction notes

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