Reaction #48756

Reaction equation

(2R,5R)-2-cyclohexylmethoxy-5-[(1S,2S)-3-(3,5-difluorophenyl)-2-((E)-3-dipropylcarbamoyl-2-methylacryloylamino)-1-hydroxypropyl]-morpholine-4-carboxylic acid tert-butyl ester

hydrogen chloride

diethyl ether

→

title compound

Yield 97.3%

(2R,5R)-2-Cyclohexylmethoxy-5-[(1S,2S)-3-(3,5-difluorophenyl)-2-((E)-3-dipropylcarbamoyl-2-methylacryloylamino)-1-hydroxypropyl]-morpholine-4-carboxylic acid hydrochloride

Yield 97.3%

Solvents

trifluoroacetic acid

dichloromethane

Conditions

Workup

1. 1
   Concentrationconcentrate
2. 2
   workup.DISSOLUTIONdissolve in ethyl acetate (30 mL)
3. 3
   Washwash with 1:1 saturated aqueous sodium chloride
4. 4
   Dryingsaturated aqueous sodium bicarbonate (30 mL), dry (sodium sulfate)
5. 5
   Concentrationconcentrate
6. 6
   workup.DISSOLUTIONDissolve the residue in ethyl acetate
7. 7
   Concentrationconcentrate

Procedure

Dissolve (2R,5R)-2-cyclohexylmethoxy-5-[(1S,2S)-3-(3,5-difluorophenyl)-2-((E)-3-dipropylcarbamoyl-2-methylacryloylamino)-1-hydroxypropyl]-morpholine-4-carboxylic acid tert-butyl ester (0.051 g, 0.075 mmol) in trifluoroacetic acid (1.5 mL) and stir at room temperature for 15 minutes. Dilute with dichloromethane (15 mL), concentrate, dissolve in ethyl acetate (30 mL), wash with 1:1 saturated aqueous sodium chloride:saturated aqueous sodium bicarbonate (30 mL), dry (sodium sulfate) and concentrate. Dissolve the residue in ethyl acetate and add 1 M hydrogen chloride in diethyl ether (0.20 mL, 0.20 mmol) and concentrate to give the title compound (0.045 g, 97.3%).

Source