4-Methylmorpholine → (S)-methyl 4-(tert-butoxycarbonylamino)-5-hydroxypentanoate

HRID 218405ノート

反応式

HRID 218405 の反応式
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][CH2:14][C:15]([O:17][CH3:18])=[O:16])[C:10](O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.ClC(OCC)=O.[BH4-].[Na+].OS([O-])(=O)=O.[K+]>C1COCC1.CO>[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:10][OH:11])[CH2:13][CH2:14][C:15]([O:17][CH3:18])=[O:16])=[O:7])([CH3:3])([CH3:2])[CH3:4]

参加物

8

反応物 5

HCID 79724-MethylmorpholineHCID 10928Ethyl chloroformateHCID 516920Potassium bisulfateHCID 4311764Sodium borohydrideHCID 7018756(S)-2-((tert-butoxycarbonyl)amino)-5-methoxy-5-oxopentanoic acid

生成物 1

HCID 11107667(S)-methyl 4-(tert-butoxycarbonylamino)-5-hydroxypentanoate収率 72%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a stirred solution of (S)-2-(tert-butoxycarbonylamino)-5-methoxy-5-oxopentanoic acid (35.2 g, 0.135 mol) in THF (500 mL) at −10° C. was added N-methylmorpholine (15 mL, 0.135 mol) followed by ethyl chloroformate (14.72 g, 0.135 mol). After 10 min, NaBH4 (15.37 g, 0.405 mol) was added in one portion. MeOH (1200 mL) was then added dropwise to the mixture over a period of 20 min at 0° C. The solution was stirred for an additional 20 min and then neutralized with 1M KHSO4. The organic solvent was removed and the aqueous layer was extracted with EtOAc (3×500 ml). The combined organic phases were washed consecutively with 1M KHSO4 (300 mL), H2O (300 mL), 5% aqueous NaHCO3 (300 mL), and dried (Na2SO4). The solvent was evaporated to give a residue, which was purified by column chromatography to give the desired (S)-methyl 4-(tert-butoxycarbonylamino)-5-hydroxypentanoate (24 g, 72%)

後処理

  1. customThe organic solvent was removed
  2. extractionthe aqueous layer was extracted with EtOAc (3×500 ml)
  3. washThe combined organic phases were washed consecutively with 1M KHSO4 (300 mL), H2O (300 mL), 5% aqueous NaHCO3 (300 mL)
  4. dry with materialdried (Na2SO4)
  5. customThe solvent was evaporated
  6. customto give a residue, which
  7. customwas purified by column chromatography

出典と根拠

ORDレコード
ord-2148c40c76da437da6fc6cc503723166
出典データセット
uspto-grants-2012_06
特許番号
US08198453B2

反応ノート

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