Triethylamine → 1-[2-(4-Isobutyl-3-trifluoromethyl-phenyl)-benzooxazol-6-ylmethyl]-azetidine-3-carboxylic acid

HRID 2353361Notes

Reaction equation

[CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[O:12][C:13]3[CH:19]=[C:18]([CH2:20]O)[CH:17]=[CH:16][C:14]=3[N:15]=2)=[CH:7][C:6]=1[C:22]([F:25])([F:24])[F:23])[CH:2]([CH3:4])[CH3:3].[NH:26]1[CH2:29][CH:28]([C:30]([OH:32])=[O:31])[CH2:27]1.CCN(CC)CC.[BH3-]C#N.[Na+]>O1CCOCC1.O=[Mn]=O>[CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[O:12][C:13]3[CH:19]=[C:18]([CH2:20][N:26]4[CH2:29][CH:28]([C:30]([OH:32])=[O:31])[CH2:27]4)[CH:17]=[CH:16][C:14]=3[N:15]=2)=[CH:7][C:6]=1[C:22]([F:24])([F:25])[F:23])[CH:2]([CH3:4])[CH3:3]

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of [2-(4-isobutyl-3-trifluoromethyl-phenyl)-benzooxazol-6-yl]-methanol (1 eq) in dioxane (0.2 M) is treated with MnO2 (10 eq). The resulting mixture is refluxed for 20 minutes and filtered through celite. After concentration, the residue is redissolved in MeOH (0.2 M) and is added azetidine-3-carboxylic acid (2 eq) and Et3N (1.8 eq). The resulting mixture is heated at 50° C. for 1 hour. After cooling to room temperature, NaBH3CN (3 eq) is added in portions. The final compound is purified by preparative LCMS. 1H NMR (400 MHz, CD3OD) δ 8.49 (s, 1H), 8.38 (d, J=8.4 Hz, 1H), 7.88 (s, 1H), 7.84 (d, J=8.4 Hz, 1H), 7.66 (d, J=8.4 Hz, 1H), 7.52 (d, J=8.4 Hz, 1H), 4.57 (s, 2H), 4.34 (m, 4H), 3.70 (m, 1H), 2.76 (d, J=6.8 Hz, 2H), 2.03 (m, 1H), 0.95 (d, J=7.2 Hz, 6H). MS: (ES+): 433.2 (M+1)+.

Workup

temperatureThe resulting mixture is refluxed for 20 minutes
filtrationfiltered through celite
concentrationAfter concentration
dissolutionthe residue is redissolved in MeOH (0.2 M)
temperatureAfter cooling to room temperature
customThe final compound is purified by preparative LCMS

Sources & evidence

ORD record: ord-7403824657c64957bd6098ebbc69cbbc
Source dataset: uspto-grants-2010_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07750021B2

Reaction notes

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