Triethylamine → HCID 72959169, compound

HRID 547272Notes

Reaction equation

HRID 547272 reaction equation
[CH:1]1([C:7]2[CH:27]=[CH:26][C:10]([CH2:11][O:12][N:13]=[C:14]([C:16]3[CH:21]=[CH:20][C:19]([CH2:22]O)=[C:18]([CH2:24][CH3:25])[CH:17]=3)[CH3:15])=[CH:9][C:8]=2[C:28]([F:31])([F:30])[F:29])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH:32]1[CH2:35][CH:34]([C:36]([OH:38])=[O:37])[CH2:33]1.CCN(CC)CC.[BH3-]C#N.[Na+]>O1CCOCC1.O=[Mn]=O>[CH:1]1([C:7]2[CH:27]=[CH:26][C:10]([CH2:11][O:12][N:13]=[C:14]([C:16]3[CH:21]=[CH:20][C:19]([CH2:22][N:32]4[CH2:35][CH:34]([C:36]([OH:38])=[O:37])[CH2:33]4)=[C:18]([CH2:24][CH3:25])[CH:17]=3)[CH3:15])=[CH:9][C:8]=2[C:28]([F:29])([F:30])[F:31])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 931923-azetidinecarboxylic AcidHCID 5003444Sodium cyanoborohydrideHCID 86595997HCID 86595997, compound

Product 1

HCID 72959169HCID 72959169, compound

Reagents, catalysts & solvents 2

HCID 14801Manganese dioxideCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

To a suspension of MnO2 (10 eq) in dioxane is added 1-(3-ethyl-4-hydroxymethyl-phenyl)-ethanone O-(4-cyclohexyl-3-trifluoromethyl-benzyl)-oxime (1 eq). The resulting mixture is refluxed for 10 minutes. After filtration and concentration, the residue is dissolved in MeOH and treated with azetidine-3-carboxylic acid (2 eq) and Et3N (1.5 eq). The resulting mixture is heated at 50° C. for 30 minutes. After cooling to room temperature, NaBH3CN (3 eq) is added in portions. Purification by preparative LCMS results in 1-{4-[1-(4-cyclohexyl-3-trifluoromethyl-benzyloxyimino)-ethyl]-2-ethyl-benzyl}-azetidine-3-carboxylic acid; 1H NMR (400 MHz, CD3OD) δ 1.24 (t, 3H), 1.30-1.60 (m, 5H), 1.74-1.92 (m, 5H), 2.28 (s, 3H), 2.79 (q, 2H), 2.92 (m, 1H), 3.68 (m, 1H), 4.32 (m, 4H), 4.51 (s, 2H) 5.22 (s, 2H), 7.38 (d, 1H), 7.50-7.68 (m, 5H). MS: (ES+): 517.3 (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 1-{4-[1-(4-cyclohexyl-3-trifluoromethyl-benzyloxyimino)-ethyl]-2-ethyl-benzyl}-azetidine-3-carboxylic acid

Sources & evidence

ORD record
ord-d483d7d5840f4d2d985f5e29816ab10a
Source dataset
uspto-grants-2011_05
Patent number
US07939519B2

Reaction notes

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