HCID 178418365、化合物 → HCID 178472371、化合物

HRID 928113ノート

反応式

HRID 928113 の反応式
[Br:1][C:2]1[S:6][C:5]([C:7]([C@H:9]2[CH2:14][CH2:13][C@H:12]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:11][CH2:10]2)=[O:8])=[N:4][CH:3]=1.[CH:20]([Mg]Br)([CH3:22])[CH3:21]>C1COCC1>[Br:1][C:2]1[S:6][C:5]([C:7]([C@H:9]2[CH2:10][CH2:11][C@H:12]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:13][CH2:14]2)([OH:8])[CH:20]([CH3:22])[CH3:21])=[N:4][CH:3]=1

参加物

4

反応物 2

HCID 178418365HCID 178418365、化合物HCID 178472369HCID 178472369、化合物

生成物 1

HCID 178472371HCID 178472371、化合物

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

A solution of ethyl trans-4-[(5-bromo-1,3-thiazol-2-yl)carbonyl]cyclohexanecarboxylate (800 mg, 2.31 mmol) in anhydrous THF (16 ml) was treated dropwise over 1 h with isopropylmagnesium bromide (2.31 mmol, 2 M, 1.15 mL) at 0° C. under a nitrogen atmosphere. After stirring at 0° C. for 15 min, the reaction was allowed to reach room temperature. After 1 h, the reaction mixture was quenched with saturated ammonium chloride and taken up in ethyl acetate, washed with brine and dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel (0% to 20% EtOAc in hexanes) and then by preparative HPLC reverse phase (C-18) eluting with 55% to 100% water in acetonitrile (0.1% trifluoroacetic acid). The collected fractions were diluted with ethyl acetate and washed with saturated sodium bicarbonate, brine, dried over magnesium sulfate, filtered and concentrated in vacuo to afford racemic ethyl trans-4-[1-(5-bromo-1,3-thiazol-2-yl)-1-hydroxy-2-methylpropyl]cyclohexanecarboxylate as a white solid. MS ESI calc'd. for C16H24BrNO3S [M+H]+ 390, 392. found 390, 392. 1H NMR (500 MHz, CDCl3) δ 7.60 (s, 1H), 4.10 (q, J=7.1, 2H), 2.30-2.20 (m, 1H), 2.17-2.06 (m, 1H), 2.05-1.79 (m, 2H), 1.93-1.81 (m, 1H), 1.62-1.50 (m, 1H), 1.48-1.20 (m, 5H), 1.22 (t, J=7.1, 3H), 0.88 (d, J=9.8, 3H), 0.87 (d, J=9.8, 3H).

後処理

  1. customto reach room temperature
  2. waitAfter 1 h
  3. customthe reaction mixture was quenched with saturated ammonium chloride
  4. washwashed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by chromatography on silica gel (0% to 20% EtOAc in hexanes)
  9. washby preparative HPLC reverse phase (C-18) eluting with 55% to 100% water in acetonitrile (0.1% trifluoroacetic acid)
  10. additionThe collected fractions were diluted with ethyl acetate
  11. washwashed with saturated sodium bicarbonate, brine
  12. dry with materialdried over magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-ff886c0ca1834de5abb04754d2a79b23
出典データセット
uspto-grants-2016_03
特許番号
US09290490B2

反応ノート

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