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

HRID 547270
Notes
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Reaction equation

HRID 547270 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
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 239Beta-AlanineHCID 8471TriethylamineHCID 4311764Sodium borohydrideHCID 865959961-(4-hydroxymethyl-phenyl)-ethanone O-(2-trifluoromethyl-biphenyl-4-ylmethyl)-oxime

Product 1

HCID 729544163-{4-[1-(2-Trifluoromethyl-biphenyl-4-ylmethoxyimino)-ethyl]-benzylamino}-propionic acid

Reagents, catalysts & solvents 2

HCID 14801Manganese dioxideCatalyst
HCID 312751,4-DioxaneSolvent

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

  1. temperatureThe resulting mixture is refluxed for 10 minutes
  2. filtrationAfter filtration and concentration
  3. dissolutionthe residue is dissolved in MeOH
  4. temperatureAfter cooling to room temperature
  5. customPurification by preparative LCMS
  6. 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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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes