Potassium bisulfate → [(3R*,4R*,5S*)-5-(3-Fluoro-4-nitro-benzyl)-4-hydroxy-tetrahydro-thiopyran-3-yl]-carbamic acid tert-butyl ester

HRID 420266ノート

反応式

HRID 420266 の反応式
[B-].[B-].C1CCOCC1.C1CCOCC1.[Ca+2].[C:16]([O:20][C:21](=[O:41])[NH:22][C@@H:23]1[C:28](=[O:29])[C@H:27]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([N+:37]([O-:39])=[O:38])=[C:33]([F:40])[CH:32]=2)[CH2:26][S:25][CH2:24]1)([CH3:19])([CH3:18])[CH3:17].OS([O-])(=O)=O.[K+]>C1COCC1>[C:16]([O:20][C:21](=[O:41])[NH:22][C@@H:23]1[C@H:28]([OH:29])[C@H:27]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([N+:37]([O-:39])=[O:38])=[C:33]([F:40])[CH:32]=2)[CH2:26][S:25][CH2:24]1)([CH3:19])([CH3:17])[CH3:18]

参加物

5

反応物 3

HCID 516920Potassium bisulfateHCID 57386559HCID 57386559、化合物HCID 90478304CID 90478304

生成物 1

HCID 68553360[(3R*,4R*,5S*)-5-(3-Fluoro-4-nitro-benzyl)-4-hydroxy-tetrahydro-thiopyran-3-yl]-carbamic acid tert-butyl ester

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-40 °C

実験手順

To a solution of calcium borohydride bis-THF complex (1.14 g, 4.6 mmol) in anhydrous THF (100 mL) was added under argon a solution of [(3R*,5S*)-5-(3-fluoro-4-nitro-benzyl)-4-oxo-tetrahydro-thiopyran-3-yl]-carbamic acid tert-butyl ester (1.77 g, 4.6 mmol) in THF (50 mL) at −70° C. The reaction mixture was slowly warmed to −40° C. and stirred for 1 h at −40° C. The reaction mixture was poured onto a cold aq. KHSO4 solution and the product was extracted with EtOAc. Combined extracts were washed with NaHCO3 solution and brine, dried over MgSO4 and evaporated. The mixture of diastereoisomers was separated by flash-chromatography on silica gel (toluene-EtOAc 6:1 to 3:1) to yield the undesired [(3R*,4S*,5S*)-diastereoisomer and the desired [(3R*,4R*,5S*)-diastereoisomer after crystallization from EtOH as a white crystalline solid: TLC (toluene-EtOAc 3:1) Rf=0.20; HPLC RtA=1.94 min; ESIMS [M+H-isobutylene]+=331; 1H NMR (600 MHz, DMSO-d6): δ 8.09 (t, 1H), 7.41 (d, 1H), 7.27 (d, 1H), 6.67 (d, 1H), 4.94 (d, 1H), 3.42 (m, 1H), 3.27 (dd, 1H), 2.91 (m, 1H), 2.55 (m, 2H), 2.39 (dd, 1H), 2.24 (m, 2H), 1.93 (m, 1H), 1.37 (s, 9H).

後処理

  1. extractionthe product was extracted with EtOAc
  2. washCombined extracts were washed with NaHCO3 solution and brine
  3. dry with materialdried over MgSO4
  4. customevaporated
  5. additionThe mixture of diastereoisomers
  6. customwas separated by flash-chromatography on silica gel (toluene-EtOAc 6:1 to 3:1)
  7. customto yield the undesired [(3R*,4S*,5S*)-diastereoisomer
  8. customafter crystallization from EtOH as a white crystalline solid
  9. customHPLC RtA=1.94 min

出典と根拠

ORDレコード
ord-1bcceaaef24f47afaa5ddee49970029c
出典データセット
uspto-grants-2012_01
特許番号
US08093406B2

反応ノート

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