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Triethylamine → Ethyl(1R,2R,3S,6S)-3-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-2-(4-fluorophenyl)-6-(hydroxymethyl)cyclohexanecarboxylate

HRID 2245247
ノート
印刷プレビュー

反応式

HRID 2245247 の反応式
[F:1][C:2]([F:38])([F:37])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@H:16]2[CH2:21][CH2:20][C@H:19]([C:22](O)=[O:23])[C@@H:18]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[C@@H:17]2[C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.ClC(OCC(C)C)=O.C(N(CC)CC)C>C1COCC1>[F:37][C:2]([F:1])([F:38])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@H:16]2[CH2:21][CH2:20][C@H:19]([CH2:22][OH:23])[C@@H:18]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[C@@H:17]2[C:30]2[CH:31]=[CH:32][C:33]([F:36])=[CH:34][CH:35]=2)[CH3:14])[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 86628111HCID 86628111、化合物

生成物 1

HCID 86628112Ethyl(1R,2R,3S,6S)-3-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-2-(4-fluorophenyl)-6-(hydroxymethyl)cyclohexanecarboxylate収率 68.3%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

To a solution of intermediate carboxylic acid (2.7 g, 4.91 mmol) from Step A in 60 mL THF was added isobutyl chloroformate (0.96 mL, 7.32 mmol) and triethyl amine (1.23 mL, 8.84 mmol). The mixture was stirred at 0° C. for 0.5 hr then at room temperature for 0.5 hr. The white precipitate was filtered and the solid was washed with dry THF. The filtrate was added to a suspension of 1 g NaBH4 in 3 mL water at 0° C. The resulting mixture was stirred at room temperature for 16 hr, quenched with 2 N aq. HCl (20 mL), then diluted with ethyl acetate (50 mL). The organic layer was separated and the aqueous was extracted with ethyl acetate (2×60 mL). The combined organic extract was washed with brine, dried over MgSO4, filtered and the solvent was removed under vacuum. The residue was purified by column chromatography (2:1 hexane:ethyl acetate) to give the title compound (1.8 g). 1H-NMR (CDCl3) δ: 7.71 (1H, s), 7.20 (2H, s), 7.00 (2H, m), 6.85 (2H, m), 4.45 (1H, q, J=6.4 Hz), 3.83 (2H, m), 3.55 (2H, m), 3.35 (1H, m), 2.93 (1H, t, J=11.0 Hz), 2.47 (1H, t, J=11.0Hz), 2.37 (1H, s), 2.33 (1H, m), 1.97 (2H, m), 1.62-1.50 (2H, m), 1.20 (1H, m), 1.33 (3H, d, J=6.4 Hz), 0.90 (3H, t, J=7.1 Hz).

後処理

  1. waitat room temperature for 0.5 hr
  2. filtrationThe white precipitate was filtered
  3. washthe solid was washed with dry THF
  4. additionThe filtrate was added to a suspension of 1 g NaBH4 in 3 mL water at 0° C
  5. stirringThe resulting mixture was stirred at room temperature for 16 hr
  6. customquenched with 2 N aq. HCl (20 mL)
  7. additiondiluted with ethyl acetate (50 mL)
  8. customThe organic layer was separated
  9. extractionthe aqueous was extracted with ethyl acetate (2×60 mL)
  10. extractionThe combined organic extract
  11. washwas washed with brine
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. customthe solvent was removed under vacuum
  15. customThe residue was purified by column chromatography (2:1 hexane:ethyl acetate)

出典と根拠

ORDレコード
ord-ce30817de4bd43b4804db87b1a5fa9b8
出典データセット
uspto-grants-2010_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07683068B2

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート