Potassium Hydroxide → 4-(4-(3-chloro-4-fluorophenyl)-1-(2-(dimethylamino)ethyl)-1H-imidazol-2-yl)piperidine-1-carboxylic acid tert-butyl ester

HRID 1685142Notes

Reaction equation

Cl.Cl[CH2:3][CH2:4][N:5]([CH3:7])[CH3:6].[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][CH:18]([C:21]2[NH:22][CH:23]=[C:24]([C:26]3[CH:31]=[CH:30][C:29]([F:32])=[C:28]([Cl:33])[CH:27]=3)[N:25]=2)[CH2:17][CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9].[OH-].[K+]>CS(C)=O.C(Cl)Cl>[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][CH:18]([C:21]2[N:22]([CH2:3][CH2:4][N:5]([CH3:7])[CH3:6])[CH:23]=[C:24]([C:26]3[CH:31]=[CH:30][C:29]([F:32])=[C:28]([Cl:33])[CH:27]=3)[N:25]=2)[CH2:17][CH2:16]1)=[O:14])([CH3:11])([CH3:9])[CH3:10]

Participants

Conditions

Temperature: 50 °C

Procedure

Add (2-chloro-ethyl)-dimethyl-amine hydrochloride (1.10 equiv; 579 μmol; 83 mg) in one portion to a mixture of 4-[4-(3-chloro-4-fluoro-phenyl)-1H-imidazol-2-yl]-piperidine-1-carboxylic acid tert-butyl ester (1 equiv; 526 μmol; 200 mg) and powdered KOH (2.5 equiv; 1.316 mmol; 73.8 mg) in DMSO (3 mL). Warm to 50° C. and stir for 2 h. Dilute with DCM, wash with water, brine, dry over MgSO4, filter, evaporate and purify on 40 g silica gel with 10% methanol/ACN to provide the title compound (194 mg; 0.43 mmol; 82%). MS (ES+): m/z=451 (M+H).

Workup

washwash with water, brine
dry with materialdry over MgSO4
filtrationfilter
customevaporate
custompurify on 40 g silica gel with 10% methanol/ACN

Sources & evidence

ORD record: ord-1f1b3834ef7a4de8b3440d5cb90ef0f8
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08148387B2

Reaction notes

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