Tetrahydrofuran → (3-Hydroxymethyl-piperidin-1-yl)-[5-(4-methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophen-2-yl]-methanone

HRID 1514121노트

반응식

HRID 1514121 반응식
[F:1][C:2]([F:18])([F:17])[C:3]1[O:7][N:6]=[C:5]([C:8]2[S:12][C:11]([C:13]([OH:15])=O)=[CH:10][CH:9]=2)[C:4]=1[CH3:16].[NH:19]1[CH2:24][CH2:23][CH2:22][CH:21]([CH2:25][OH:26])[CH2:20]1.C1COCC1.N1CCCCC1>C(N(CC)CC)C>[OH:26][CH2:25][CH:21]1[CH2:22][CH2:23][CH2:24][N:19]([C:13]([C:11]2[S:12][C:8]([C:5]3[C:4]([CH3:16])=[C:3]([C:2]([F:1])([F:18])[F:17])[O:7][N:6]=3)=[CH:9][CH:10]=2)=[O:15])[CH2:20]1

참가 물질

6

반응물 4

HCID 8028TetrahydrofuranHCID 8082PiperidineHCID 107308Piperidin-3-ylmethanolHCID 252109975-(4-Methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophene-2-carboxylic acid

생성물 1

HCID 25211606(3-Hydroxymethyl-piperidin-1-yl)-[5-(4-methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophen-2-yl]-methanone

시약·촉매·용매 1

HCID 8471Triethylamine용매

실험 절차

Prepared from 5-(5-Trifluoromethyl-4-methyl-isoxazol-3-yl)-thiophene-2-carboxylic acid and 3-piperdinemethanol by the method described in Example 2 Method B reversing the order of addition such that solid acid chloride was added to a THF solution of triethylamine and piperdine derivative. The reaction mixture was evaporated to an oil then partitioned between EtOAc (5 mL) and water (5 mL). The organic fraction was further washed with brine (2×5 mL), dried over MgSO4, filtered, and evaporated to an oil. The crude product was then chromatographed on silica gel with EtOAc/hexanes (75%) as eluant to (190 mg, 75%). 1H NMR (CDCl3) 1.28-1.35 (m, 1 H), 1.44-1.56 (m, 1 H), 1.67-1.82 (m, 3 H), 2.28 (d, J=0.9, 3 H), 2.99 (dd, J=13.2, 9.7, 1 H), 3.32 (br s, 1 H), 3.41-3.52 (m, 2 H), 4.10 (br s, 1 H), 4.21 (d, J=11.4, 1 H), 7.29 (d, J=4.0, 1 H), 7.37 (d, J=4.0, 1 H). 13C NMR 7.8, 24.9, 27.2, 39.1, ˜49 (br), 64.5, 114.8, 118.7 (q, J=271), 128.1, 129.3, 131.2, 140.3, 155.0 (q, J=40), 157.9, 162.9. 19F NMR −63.2. LC/MS 5.91 min, [M+1]+ 375.

후처리

  1. customThe reaction mixture was evaporated to an oil
  2. customthen partitioned between EtOAc (5 mL) and water (5 mL)
  3. washThe organic fraction was further washed with brine (2×5 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated to an oil
  7. customThe crude product was then chromatographed on silica gel with EtOAc/hexanes (75%) as eluant to (190 mg, 75%)
  8. customLC/MS 5.91 min, [M+1]+ 375

출처 및 근거

ORD 기록
ord-e1e126b13e1c4292996f82a378c026f7
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08222243B2

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