Benzyl Bromide → [[(2R,3R,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-(2,2-difluoroethoxy)phenyl]methyl]phenyl]-6-methoxy-tetrahydropyran-2-yl]methoxy]tert-butyl-dimethyl-silane

HRID 1913073ノート

反応式

HRID 1913073 の反応式
[H-].[Na+].[Si:3]([O:10][CH2:11][C@H:12]1[O:17][C@:16]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([O:34][CH2:35][CH:36]([F:38])[F:37])=[CH:30][CH:29]=3)[CH:21]=2)([O:18][CH3:19])[C@H:15]([OH:39])[C@@H:14]([OH:40])[C@@H:13]1[OH:41])([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4].[CH2:42](Br)[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>C1COCC1.CN(C)C=O>[CH2:42]([O:41][C@H:13]1[C@H:14]([O:40][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C@@H:15]([O:39][CH2:16][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C@@:16]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([CH2:27][C:28]3[CH:29]=[CH:30][C:31]([O:34][CH2:35][CH:36]([F:38])[F:37])=[CH:32][CH:33]=3)[CH:21]=2)([O:18][CH3:19])[O:17][C@@H:12]1[CH2:11][O:10][Si:3]([C:6]([CH3:8])([CH3:9])[CH3:7])([CH3:5])[CH3:4])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1

参加物

6

反応物 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 86685167(2S,3R,4S,5S,6R)-6-[(tert-butyl(dimethyl)silyl)oxymethyl]-2-[4-chloro-3-[[4-(2,2-difluoroethoxy)phenyl]methyl]phenyl]-2-methoxy-tetrahydropyran-3,4,5-triol

生成物 1

HCID 86685168[[(2R,3R,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-(2,2-difluoroethoxy)phenyl]methyl]phenyl]-6-methoxy-tetrahydropyran-2-yl]methoxy]tert-butyl-dimethyl-silane収率 200.1%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

60% NaH (1.9 g, 47.21 mmol) and 15 mL THF were added into a 100 mL reaction flask and cooled to 0° C., followed by dropwise addition of (2S,3R,4S,5S,6R)-6-[(tert-butyl(dimethyl)silyl)oxymethyl]-2-[4-chloro-3-[[4-(2,2-difluoroethoxy)phenyl]methyl]phenyl]-2-methoxy-tetrahydropyran-3,4,5-triol 12f (4.96 g, 8.43 mmol) in THF (18 mL) within 10 minutes at 0° C. The reaction mixture was stirred for 30 minutes. Then a solution of benzyl bromide (7.21 g, 42.15 mmol) in N,N-dimethyl formamide (10 mL) was dropwise added before the reaction mixture was warmed and stirred for 16 hours at room temperature. Thereafter, the reaction mixture was partitioned after 200 mL ethyl acetate, saturated sodium bicarbonate (70 mL) and water (50 mL) were added. The organic extract was washed with 0.01 N hydrochloric acid (60 mL) and saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure to obtain the title compound [[(2R,3R,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-(2,2-difluoroethoxy)phenyl]methyl]phenyl]-6-methoxy-tetrahydropyran-2-yl]methoxy]tert-butyl-dimethyl-silane 12g (7.25 g, pale yellow liquid), which was used directly in the next step without purification.

後処理

  1. temperaturewas warmed
  2. stirringstirred for 16 hours at room temperature
  3. customThereafter, the reaction mixture was partitioned after 200 mL ethyl acetate, saturated sodium bicarbonate (70 mL) and water (50 mL)
  4. additionwere added
  5. extractionThe organic extract
  6. washwas washed with 0.01 N hydrochloric acid (60 mL) and saturated sodium chloride solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated under reduced pressure

出典と根拠

ORDレコード
ord-1ac8e3ace81e40ee91197135a556e354
出典データセット
uspto-grants-2013_12
特許番号
US08609622B2

反応ノート

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