Beta-Alanine → 3-{4-[1-(2-Trifluoromethyl-biphenyl-4-ylmethoxyimino)-ethyl]-benzylamino}-propionic acid

HRID 547270Notes

Reaction equation

[F:1][C:2]([F:29])([F:28])[C:3]1[CH:8]=[C:7]([CH2:9][O:10][N:11]=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([CH2:20]O)=[CH:16][CH:15]=2)[CH3:13])[CH:6]=[CH:5][C:4]=1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.[NH2:30][CH2:31][CH2:32][C:33]([OH:35])=[O:34].CCN(CC)CC.[BH4-].[Na+]>O1CCOCC1.O=[Mn]=O>[F:1][C:2]([F:28])([F:29])[C:3]1[CH:8]=[C:7]([CH2:9][O:10][N:11]=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([CH2:20][NH:30][CH2:31][CH2:32][C:33]([OH:35])=[O:34])=[CH:16][CH:15]=2)[CH3:13])[CH:6]=[CH:5][C:4]=1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a suspension of MnO2 (10 eq) in dioxane is added 1-(4-hydroxymethyl-phenyl)-ethanone O-(2-trifluoromethyl-biphenyl-4-ylmethyl)-oxime (1 eq). The resulting mixture is refluxed for 10 minutes. After filtration and concentration, the residue is dissolved in MeOH and treated with β-alanine (2 eq) and Et3N (1.5 eq). The resulting mixture is heated at 50° C. for 30 minutes. After cooling to room temperature, NaBH4 (3 eq) is added in portions. Purification by preparative LCMS results in 3-{4-[1-(2-trifluoromethyl-biphenyl-4-ylmethoxyimino)-ethyl]-benzylamino}-propionic acid; 1H NMR (400 MHz, CD3OD) δ 2.28 (s, 3H), 2.75 (t, J=6.8 Hz, 2H), 3.26 (t, J=6.8 Hz, 2H), 4.22 (s, 2H), 5.30 (s, 2H), 7.26-7.77 (m, 12H). MS: (ES+): 471.1 (M+1)+.

Workup

temperatureThe resulting mixture is refluxed for 10 minutes
filtrationAfter filtration and concentration
dissolutionthe residue is dissolved in MeOH
temperatureAfter cooling to room temperature
customPurification by preparative LCMS
customresults in 3-{4-[1-(2-trifluoromethyl-biphenyl-4-ylmethoxyimino)-ethyl]-benzylamino}-propionic acid

Sources & evidence

ORD record: ord-30d51bc7ec8f4b26a81dc0207b82733e
Source dataset: uspto-grants-2011_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07939519B2

Reaction notes

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