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

HRID 629694Notes

Reaction equation

HRID 629694 reaction equation
[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

Participants

8

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent3×HCID 1140TolueneSolvent2×HCID 25517Ammonium ChlorideSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-874dedb56d9345328271d55a042551a6
Source dataset
uspto-grants-2016_04
Patent number
US09315475B2

Reaction notes

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