(-)-Epichlorohydrin → ((2S,5S)-4-Benzyl-5-(((tert-butyldimethylsilyl)oxy)methyl)morpholin-2-YL)methanol

HRID 629694ノート

反応式

HRID 629694 の反応式
[CH2:1]([NH:8][C@H:9]([CH2:12][O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[CH2:10][OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:21]([C@@H:23]1[O:25][CH2:24]1)Cl.Cl([O-])(=O)(=O)=O.[Li+].C[O-].[Na+]>C1(C)C=CC=CC=1.CO.[NH4+].[Cl-]>[CH2:1]([N:8]1[C@H:9]([CH2:12][O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:15])[CH3:16])[CH2:10][O:11][C@H:23]([CH2:24][OH:25])[CH2:21]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

8

反応物 4

HCID 2734062(-)-EpichlorohydrinHCID 10942334Sodium Methoxide2 回HCID 11770896(2S)-2-(benzylamino)-3-{[tert-butyl(dimethyl)silyl]oxy}propan-1-olHCID 23665649Lithium perchlorate

生成物 1

HCID 86726300((2S,5S)-4-Benzyl-5-(((tert-butyldimethylsilyl)oxy)methyl)morpholin-2-YL)methanol

試薬・触媒・溶媒 3

HCID 887Methanol溶媒3 回HCID 1140Toluene溶媒2 回HCID 25517Ammonium Chloride溶媒

実験手順

To (2S)-2-(benzylamino)-3-{[tert-butyl(dimethyl)silyl]oxy}propan-1-ol (1 eq) in Toluene (0.3 M) at rt was added (R)-(−)-epichlorohydrin (1.3 eq.) and Lithium perchlorate (1.3 eq) was then slowly added over 2 hours. The mixture was stirred at rt for 48 hrs and sodium methoxide (2.5 eq of a 25% solution of NaOMe in MeOH) was added. MeOH was then added to the reaction mixture to obtain a 4:1 ratio of toluene:MeOH as solvent. The reaction mixture was stirred for 48 hrs at rt and diluted with saturated aqueous NH4Cl. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by automated SiO2 flash chromatography system using solvent gradient of 0% EtOAc/Hex to 25% EtOAc/Hex to afford the desired compound.

後処理

  1. additionwas then slowly added over 2 hours
  2. stirringThe reaction mixture was stirred for 48 hrs at rt
  3. extractionThe aqueous layer was extracted with EtOAc
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by automated SiO2 flash chromatography system

出典と根拠

ORDレコード
ord-874dedb56d9345328271d55a042551a6
出典データセット
uspto-grants-2016_04
特許番号
US09315475B2

反応ノート

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