Sodium Sulfite → Ethyl (2R)-4-{4'-[(di-tert-butoxyphosphoryl)oxy]biphenyl-4-yl}-2-methyl-2-(methylsulfonyl)butanoate

HRID 533538

反応式

HRID 533538 の反応式
N1C=NN=N1.[C:6]([O:10][P:11](N(C(C)C)C(C)C)[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:9])([CH3:8])[CH3:7].[OH:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[CH:36]=[CH:35][C:34]([CH2:37][CH2:38][C@@:39]([CH3:49])([S:45]([CH3:48])(=[O:47])=[O:46])[C:40]([O:42][CH2:43][CH3:44])=[O:41])=[CH:33][CH:32]=2)=[CH:27][CH:26]=1.S([O-])([O-])=[O:51].[Na+].[Na+]>O1CCCC1>[C:13]([O:12][P:11]([O:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[CH:36]=[CH:35][C:34]([CH2:37][CH2:38][C@@:39]([CH3:49])([S:45]([CH3:48])(=[O:47])=[O:46])[C:40]([O:42][CH2:43][CH3:44])=[O:41])=[CH:33][CH:32]=2)=[CH:27][CH:26]=1)([O:10][C:6]([CH3:7])([CH3:8])[CH3:9])=[O:51])([CH3:14])([CH3:15])[CH3:16]

参加物

6

反応物 4

HCID 24437Sodium SulfiteHCID 853005Di-tert-butyl N,N-DiisopropylphosphoramiditeHCID 66579462Ethyl (2R)-4-(4'-hydroxybiphenyl-4-yl)-2-methyl-2-(methylsulfonyl)butanoateHCID 178418441HCID 178418441、化合物

生成物 1

HCID 66577870Ethyl (2R)-4-{4'-[(di-tert-butoxyphosphoryl)oxy]biphenyl-4-yl}-2-methyl-2-(methylsulfonyl)butanoate収率 91%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

A solution of 1H-tetrazole (2.37 g, 33.9 mmol, 3.0 equiv), di-tert-butyl-N,N-diisopropylphosphoramidite (7.42 mL, 22.6 mmol, 2.0 equiv), and ethyl(2R)-4-(4′-hydroxybiphenyl-4-yl)-2-methyl-2-(methylsulfonyl)butanoate (4.25 g, 11.3 mmol, 1.0 equiv) in tetrahydrofuran (113 mL) was allowed to stir overnight at room temperature. A solution of saturated sodium sulfite (330 mL) was added, and the mixture was extracted with dichloromethane (3×440 mL). The combined organic layers were washed with water (3×330 mL), brine (3×330 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel (50% ethyl acetate in heptane) to provide a colorless oil (5.84 g, 91%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.33 (t, J=7.13 Hz, 3H) 1.50-1.52 (m, 18H) 1.71 (s, 3H) 2.17-2.30 (m, 1H) 2.46-2.61 (m, 2H) 2.72-2.85 (m, 1H) 3.04 (s, 3H) 4.26 (qd, J=7.13, 1.27 Hz, 2H) 7.21-7.28 (m, 4H) 7.45-7.53 (m, 4H).

後処理

  1. extractionthe mixture was extracted with dichloromethane (3×440 mL)
  2. washThe combined organic layers were washed with water (3×330 mL), brine (3×330 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude material was purified by flash chromatography on silica gel (50% ethyl acetate in heptane)

出典と根拠

ORDレコード
ord-be947402c8f94724b7e6e7a24b3b420b
出典データセット
uspto-grants-2014_10
特許番号
US08853258B2

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