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

HRID 1514121ノート

反応式

HRID 1514121 の反応式
[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

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8471Triethylamine溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-e1e126b13e1c4292996f82a378c026f7
出典データセット
uspto-grants-2012_07
特許番号
US08222243B2

反応ノート

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