1,2-Dichloroethane → 4-(5-(4-(2-(S)-Butoxy)-3-trifluoromethylphenyl)-1,2,4-oxadiazol-3-yl)phenylmethanol

HRID 1268927Notes

Reaction equation

[F:1][C:2]([F:18])([F:17])[C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][C@H:13]([CH2:15][CH3:16])[CH3:14])[C:6]([OH:8])=O.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CC(C)CC1C=CC(C2O[N:45]=[C:44]([C:47]3[CH:52]=[CH:51][C:50]([CH2:53][OH:54])=[CH:49][CH:48]=3)[N:43]=2)=CC=1>CN(C=O)C>[CH3:14][C@H:13]([O:12][C:11]1[CH:10]=[CH:9][C:5]([C:6]2[O:8][N:45]=[C:44]([C:47]3[CH:52]=[CH:51][C:50]([CH2:53][OH:54])=[CH:49][CH:48]=3)[N:43]=2)=[CH:4][C:3]=1[C:2]([F:1])([F:18])[F:17])[CH2:15][CH3:16]

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of 600 mg (2.2 mmol) of 3-trifluoromethyl-4-(2-(S)-methylpropyloxy)benzoic acid (from Step B), 542 mg (2.2 mmol) of EDC and 357 mg (2.2 mmol) of HOBT in 6 mL of DMF were stirred at rt for 1 h. The reaction was subsequently treated with 350 mg (2.2 mmol) of N-hydroxy-4-(hydroxymethyl)benzamidine (from Aldehyde 1, Step A) and heated to 80° C. for 12 h. The reaction mixture was cooled and purified via chromatography on a Biotage 40M cartridge using 2:1 v/v hexanes/EtOAc as the eluant affording 510 mg of the title compound: 1H NMR (500 MHz) δ 1.01 (t, J=7.3, 3H), 1.38 (d, J=5.9, 3H), 1.73–1.83 (m, 2H), 4.55 (septet, 1H), 4.79 (s, 2H), 7.12 (d, J=8.9, 1H), 7.51 (d, J=8.2, 2H), 8.15 (d, J=8.2, 2H), 8.30 (d, J=8.9, 1H), 8.43 (s, 1H).

Workup

temperatureThe reaction mixture was cooled
custompurified via chromatography on a Biotage 40M cartridge

Sources & evidence

ORD record: ord-84eafe5f5aa941e6b700810d5927da87
Source dataset: uspto-grants-2007_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07199142B2

Reaction notes

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