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

HRID 2220274Notes

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-3eb5fd9b30de4fd895cb897504dc6cb2
Source dataset: uspto-grants-2008_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07417065B2

Reaction notes

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