Benzylethanolamine → (S)-(4-benzylmorpholin-2-yl)methanol

HRID 1524179Notes

Reaction equation

HRID 1524179 reaction equation
C([C@@H]1[O:5][CH2:4]1)Cl.[CH2:6]([NH:13][CH2:14][CH2:15][OH:16])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.O.[CH:18](O)(C)[CH3:19].[OH-].C([N+](CC)(CC)CC)C>O>[CH2:6]([N:13]1[CH2:19][CH2:18][O:16][C@H:15]([CH2:4][OH:5])[CH2:14]1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

6

Reactant 4

HCID 4348BenzylethanolamineHCID 6509Tetraethylammonium HydroxideHCID 2734062(-)-EpichlorohydrinHCID 21889133Propan-2-ol--water (1/1)

Product 1

HCID 736507(S)-(4-benzylmorpholin-2-yl)methanolYield 52%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

(R)-epichlorohydrin (1.7 ml, 21.6 mmol) was added to a solution of N-benzylethanolamine (3.73 ml, 25.7 mmol) in 1:1 water/isopropanol (7 ml), keeping the temperature between 20 and 25° C. After 6 hours the milky suspension was stored at −20° C. overnight. The solution was warmed to room temperature and 40% tetraethylammonium hydroxide (TEAOH) in water (12.3 ml) was added. The mixture was stirred at 20° C. for 1 hour and then quenched with 1M HCl (4 ml), keeping the pH around 10. The suspension was diluted with water (7 ml) and extracted with dichloromethane (DCM; 3×13 ml). The combined organic portions were dried and concentrated. The residue (yellowish oil) was purified by flash chromatography eluting the silica with DCM/MeOH 1:0 to 92:8. The product was isolated from the low Rf (slow-eluting) fraction as a colourless oil (2.3 g; 52% yield).

Workup

  1. customthe temperature between 20 and 25° C
  2. customquenched with 1M HCl (4 ml)
  3. additionThe suspension was diluted with water (7 ml)
  4. extractionextracted with dichloromethane (DCM; 3×13 ml)
  5. customThe combined organic portions were dried
  6. concentrationconcentrated
  7. customThe residue (yellowish oil) was purified by flash chromatography
  8. washeluting the silica with DCM/MeOH 1:0 to 92:8
  9. customThe product was isolated from the low Rf (slow-eluting) fraction as a colourless oil (2.3 g; 52% yield)

Sources & evidence

ORD record
ord-b600fd9518bf4b3cb522a8c6c3bcae70
Source dataset
uspto-grants-2015_07
Patent number
US09079895B2

Reaction notes

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