4-Methylmorpholine → (R)-(+)-3-Benzyloxy-2-(Boc-amino)-1-propanol

HRID 339480

反応式

HRID 339480 の反応式
[CH2:1]([O:8][CH2:9][C@H:10]([NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C:11](O)=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN1CCOCC1.ClC(OCC(C)C)=O.[BH4-].[Na+]>COCCOC>[CH2:1]([O:8][CH2:9][C@H:10]([NH:14][C:15](=[O:16])[O:17][C:18]([CH3:20])([CH3:19])[CH3:21])[CH2:11][OH:12])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

6

反応物 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 90234L-Serine, N-[(1,1-dimethylethoxy)carbonyl]-O-(phenylmethyl)-HCID 4311764Sodium borohydride

生成物 1

HCID 11065873(R)-(+)-3-Benzyloxy-2-(Boc-amino)-1-propanol収率 92%

試薬・触媒・溶媒 1

HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
-20 °C

実験手順

(2S)-3-(benzyloxy)-2-[(tert-butoxycarbonyl)amino]propanoic acid (7.2 g, 24.4 mmole) was dissolved in ethylene glycol dimethyl ether (50 mL). N-Methylmorpholine (2.7 ml, 24.4 mmole) was added, and the resulting clear solution was cooled to −20° C. Isobutyl chloroformate (3.19 ml, 24.4 mmole) was added dropwise to cause N-methylmorpholine HCl salt precipitation. Stirring was continued for 15 min and the supernatant was then transferred via a filter-tipped funnel into a rapidly stirred solution of NaBH4 (2.93 g, 73.2 mmole) in ice water and washed with dry DME. After the mixture was stirred for 30 min, it was extracted with EtOAc and washed with H2O. The organic layers were combined, dried over Na2SO4, and concentrated in vacuo. Purification by chromatography (silica, 4/1: Hexane/EtOAc, Rf=0.2) afforded tert-butyl N-[(1R)-2-(benzyloxy)-1-(hydroxymethyl)ethyl]carbamate as a white solid (6.3 g, 92%).

後処理

  1. customN-methylmorpholine HCl salt precipitation
  2. washwashed with dry DME
  3. stirringAfter the mixture was stirred for 30 min
  4. extractionit was extracted with EtOAc
  5. washwashed with H2O
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customPurification by chromatography (silica, 4/1: Hexane/EtOAc, Rf=0.2)

出典と根拠

ORDレコード
ord-d14da13e9cb94b56a27abd58aeadfe2b
出典データセット
uspto-grants-2014_11
特許番号
US08895497B2

関連ノート

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