Cyanomethylenetributylphosphorane → 3-[5-Chloro-2-(3-phenyl-cyclobutoxy)-phenoxy]-azetidine-1-carboxylic acid tert-butyl ester

HRID 237293Notes

Reaction equation

[C:1]1([CH:7]2[CH2:10][CH:9]([OH:11])[CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:12]([O:16][C:17]([N:19]1[CH2:22][CH:21]([O:23][C:24]2[CH:29]=[C:28]([Cl:30])[CH:27]=[CH:26][C:25]=2O)[CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].C(C=P(CCCC)(CCCC)CCCC)#N>C1(C)C=CC=CC=1>[C:12]([O:16][C:17]([N:19]1[CH2:22][CH:21]([O:23][C:24]2[CH:29]=[C:28]([Cl:30])[CH:27]=[CH:26][C:25]=2[O:11][CH:9]2[CH2:8][CH:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH2:10]2)[CH2:20]1)=[O:18])([CH3:15])([CH3:13])[CH3:14]

Participants

Conditions

Temperature: 120 °C

Procedure

The mixture of the title compound of Step A (80 mg), 3-(5-chloro-2-hydroxy-phenoxy)-azetidine-1-carboxylic acid tert-butyl ester (200 mg) and cyanomethylenetri-n-butylphosphorane (1.0 mmol) in toluene (2 mL) was heated at 120° C. in a microwave reactor for 1 h. The mixture was cooled to rt and purified via PTLC providing 3-[5-chloro-2-(3-phenyl-cyclobutoxy)-phenoxy]-azetidine-1-carboxylic acid tert-butyl ester (120 mg). The ester was re-dissolved into CH2Cl2 (10 mL), and TFA (2 mL) was added. The mixture was stirred at rt for 4 h then concentrated to give the title compound (168 mg). MS (ESI): mass calcd. for C19H20ClNO2, 329.1; m/z found, 330.1 [M+H]+. 1H NMR (MeOD): 7.26-6.64 (m, 8H), 5.30-5.15 (m, 2H), 4.95-4.83 (m, 2H), 4.60-4.52 (m, 1H), 3.78-3.65 (m, 1H), 2.68-2.58 (m, 4H).

Workup

temperatureThe mixture was cooled to rt
custompurified via PTLC

Sources & evidence

ORD record: ord-138405a4b97b4efb80ea1ad874710a0f
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08642583B2

Reaction notes

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