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Triethylamine → 1-{4-[1-(4-Cyclohexyl-3-trifluoromethyl-benzyloxyimino)-ethyl]-2-ethyl-benzyl}-azetidine-3-carboxylic acid

HRID 2405684
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HRID 2405684 반응식
[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
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참가 물질

7

반응물 4

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

생성물 1

HCID 729591691-{4-[1-(4-Cyclohexyl-3-trifluoromethyl-benzyloxyimino)-ethyl]-2-ethyl-benzyl}-azetidine-3-carboxylic acid

시약·촉매·용매 2

HCID 14801
Manganese dioxide
촉매
HCID 312751,4-Dioxane용매

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온도
50 °C

실험 절차

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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-3e6491533c9f4e8393261231c161192a
출처 데이터셋
uspto-grants-2014_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08809316B2

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