Acetic Acid → (2R,4S)-2-[(4S,5S)-3-Acetyl-4-(3,5-difluoro-benzyl)-2,2-dimethyl-oxazolidin-5-yl]-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 732595ノート

反応式

HRID 732595 の反応式
N(C(OC(C)C)=O)=NC(OC(C)C)=O.[C:15]([O:19][C:20]([N:22]1[CH2:26][C@H:25]([OH:27])[CH2:24][C@@H:23]1[C@H:28]1[O:32][C:31]([CH3:34])([CH3:33])[N:30]([C:35](=[O:37])[CH3:36])[C@H:29]1[CH2:38][C:39]1[CH:44]=[C:43]([F:45])[CH:42]=[C:41]([F:46])[CH:40]=1)=[O:21])([CH3:18])([CH3:17])[CH3:16].C(O)(=O)C.C[Si](C)(C)CCOC(=O)C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[OH-].[Na+]>O1CCCC1.C(OCC)(=O)C.O>[C:15]([O:19][C:20]([N:22]1[CH2:26][C@@H:25]([OH:27])[CH2:24][C@@H:23]1[C@H:28]1[O:32][C:31]([CH3:33])([CH3:34])[N:30]([C:35](=[O:37])[CH3:36])[C@H:29]1[CH2:38][C:39]1[CH:40]=[C:41]([F:46])[CH:42]=[C:43]([F:45])[CH:44]=1)=[O:21])([CH3:16])([CH3:17])[CH3:18]

参加物

10

反応物 6

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 2724141Tetrabutylammonium FluorideHCID 112582822-(Trimethylsilyl)ethyl 4-(diphenylphosphino)benzoateHCID 68814386(2R,4R)-2-[(4S,5S)-3-Acetyl-4-(3,5-difluorobenzyl)-2,2-dimethyloxazolidin-5-yl]-4-hydroxypyrrolidine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 68814265(2R,4S)-2-[(4S,5S)-3-Acetyl-4-(3,5-difluoro-benzyl)-2,2-dimethyl-oxazolidin-5-yl]-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester収率 95%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

Add dropwise diisopropyl azodicarboxylate (0.20 mL, 1.04 mmol) to a solution of (2R,4R)-2-[(4S,5S)-3-acetyl-4-(3,5-difluorobenzyl)-2,2-dimethyloxazolidin-5-yl]-4-hydroxypyrrolidine-1-carboxylic acid tert-butyl ester (0.314 g, 0.69 mmol), acetic acid (0.06 mL, 1.04 mmol) and 4-diphenylphosphanyl-benzoic acid 2-trimethylsilanyl-ethyl ester (0.42 g, 1.04 mmol, prepared according to Synlett 2003 (4) p 473-476) in tetrahydrofuran (3 mL). Stir solution 18 hours, then add a 1M solution of tetrabutylammonium fluoride in tetrahydrofuran (3 mL) and stir 90 minutes. Add a 1N aqueous solution of sodium hydroxide (3 mL) and stir 30 minutes. Dilute with ethyl acetate and water. Evaporate the organic layer and dissolve in methanol (30 mL). Add sodium carbonate (0.365 g) and water (1 mL) and stir 18 hours. Evaporate and partition with ethyl acetate and water, wash organic layer with saturated sodium chloride solution, dry with magnesium sulfate and purify on silica gel with hexane/ethyl acetate mixtures to give the title compound as a foam (0.295 g, 95%).

後処理

  1. stirringstir 30 minutes
  2. customEvaporate the organic layer
  3. dissolutiondissolve in methanol (30 mL)
  4. stirringAdd sodium carbonate (0.365 g) and water (1 mL) and stir 18 hours
  5. customEvaporate
  6. custompartition with ethyl acetate and water
  7. washwash organic layer with saturated sodium chloride solution
  8. dry with materialdry with magnesium sulfate
  9. custompurify on silica gel with hexane/ethyl acetate

出典と根拠

ORDレコード
ord-8eede0e995b049db9ef5802cd1fb1ee2
出典データセット
uspto-grants-2009_09
特許番号
US07585885B2

反応ノート

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