Isobutyl chloroformate → tert-butyl (3R)-3-(9H-fluoren-9-ylmethoxycarbonylamino)-4-hydroxy-butanoate

HRID 1520592ノート

反応式

HRID 1520592 の反応式
[NH:1]([C:14]([O:16][CH2:17][CH:18]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24]2[C:19]1=[CH:20][CH:21]=[CH:22][CH:23]=2)=[O:15])[C@@H:2]([C:11](O)=[O:12])[CH2:3][C:4](=[O:10])[O:5][C:6]([CH3:9])([CH3:8])[CH3:7].C(N(CC)C(C)C)(C)C.ClC(OCC(C)C)=O.[BH4-].[Na+]>C(OCC)(=O)C.CO.O1CCCC1>[CH:20]1[C:19]2[CH:18]([CH2:17][O:16][C:14]([NH:1][C@@H:2]([CH2:11][OH:12])[CH2:3][C:4]([O:5][C:6]([CH3:7])([CH3:9])[CH3:8])=[O:10])=[O:15])[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:24]=2[CH:23]=[CH:22][CH:21]=1

参加物

8

反応物 4

HCID 62365Isobutyl chloroformateHCID 81531DiisopropylethylamineHCID 4311764Sodium borohydrideHCID 70188164-tert-Butyl N-((9H-Fluoren-9-ylmethoxy)carbonyl)-D-aspartate

生成物 1

HCID 56845319tert-butyl (3R)-3-(9H-fluoren-9-ylmethoxycarbonylamino)-4-hydroxy-butanoate

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
-40 °C

実験手順

Fmoc-D-Asp(OtBu)-OH (9.0 g) and N,N-diisopropylethylamine (4.6 mL) were added to tetrahydrofuran (100 mL) and cooled to −40° C. Isobutyl chloroformate (3.1 mL) was added, and the solution was gradually warmed to 0° C. over 30 minutes. The solution was cooled to −20° C., and to it was carefully added sodium borohydride (1.64 g, 43.6 mmol) and methanol (10 mL). The solution was gradually warmed to room temperature over two hours, diluted with ethyl acetate (200 mL), washed with water (100 mL) and brine (50 mL), dried with anhydrous magnesium sulfate, filtered, and concentrated to afford crude product of sufficient purity for subsequent use.

後処理

  1. temperaturethe solution was gradually warmed to 0° C. over 30 minutes
  2. temperatureThe solution was cooled to −20° C.
  3. temperatureThe solution was gradually warmed to room temperature over two hours
  4. washwashed with water (100 mL) and brine (50 mL)
  5. dry with materialdried with anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford crude product of sufficient purity for subsequent use

出典と根拠

ORDレコード
ord-99358a111d984135b0e6ac6d8065ac52
出典データセット
uspto-grants-2015_07
特許番号
US09073855B2

反応ノート

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