HCID 178418443、化合物 → HCID 178472375、化合物

HRID 928111ノート

反応式

HRID 928111 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.[CH2:20]([Mg]Br)[CH3:21]>C1COCC1.O.CCOC(C)=O>[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])[CH2:20][CH3:21])=[N:4][CH:3]=1

参加物

6

反応物 2

HCID 178418443HCID 178418443、化合物HCID 178472369HCID 178472369、化合物

生成物 1

HCID 178472375HCID 178472375、化合物

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A solution of ethyl trans-4-[(5-bromo-1,3-thiazol-2-yl)carbonyl]cyclohexanecarboxylate (500 mg, 1.444 mmol) in THF (6 mL) was cooled to −60° C. Ethylmagnesium bromide (3.0 M in THF, 481 μl, 1.444 mmol) was added dropwise and the resulting mixture was stirred for 1 hour. The mixture was diluted with water and EtOAc and the layers were separated. The organic layer was washed with saturated sodium bicarbonate, brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (5-80% EtOAc/Hexanes) to afford racemic-trans-ethyl 4-[1-(5-bromo-1,3-thiazol-2-yl)-1-hydroxypropyl]cyclohexanecarboxylate as a yellow solid. The racemic mixture was purified by super critical fluid chromatography (Chiral Technology AD-H 2.1×25 cm, 5 uM, 30%/70% Methanol/CO2 with a 14 minute run time) to afford enantiomer 1 and enantiomer 2 as clear oils. Enantiomer 1 (retention time=7.24 min): MS ESI calc'd. for C12H22BrNO3S [M+H]+ 376, 378. found 376, 378. 1H NMR (500 MHz, DMSO-d6) δ 7.75 (s, 1H), 5.62 (s, 1H), 3.99 (q, J=7.0, 2H), 2.20-0.80 (m, 15H), 0.68 (t, J=6.9, 3H). Enantiomer 2 (retention time=10.18 min): MS ESI calcd for C17H26BrNO3S [M+H]+ 376, 378. found 376, 378. 1H NMR (500 MHz, DMSO-d6) δ 7.75 (s, 1H), 5.62 (s, 1H), 3.99 (q, J=7.0, 2H), 2.20-0.8 (m, 15H), 0.68 (t, J=6.9, 3H).

後処理

  1. customthe layers were separated
  2. washThe organic layer was washed with saturated sodium bicarbonate, brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by chromatography on silica gel (5-80% EtOAc/Hexanes)

出典と根拠

ORDレコード
ord-c63274798af145e5a5dac174e0c06efd
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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