Reaction #159338

Reaction equation

((R)-3-amino-2-hydroxy-propyl)-cyclohexylmethyl-phosphinic acid benzyl ester hydrochloride

Triethylamine

N-Boc-L-valine

HOBT

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride

→

compound

Yield 60.1%

[(R)-3-((S)-2-tert-Butoxycarbonylamino-3-methyl-butyrylamino)-2-hydroxy-propyl]-cyclohexylmethyl-phosphinic acid benzyl ester

Yield 60.1%

Solvents

ethyl acetate

DMF

DMF

Conditions

Workup

1. 1
   workup.STIRRINGthe resulting solution was stirred overnight at room temperature
2. 2
   Washwas washed with saturated NaHCO3, half saturated brine
3. 3
   DryingThe organic layer was dried over MgSO4
4. 4
   Filtrationfiltered
5. 5
   Concentrationconcentrated in vacuo
6. 6
   OtherThe residue was purified by SiO2 chromatography

Procedure

To a solution of N-Boc-L-valine (1.798 g, 7.15 mmol) and HOBT, (1.257 g, 9.30 mmol) in DMF (10 mL) under N2 was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.440 g, 7.51 mmol). The resulting clear solution was stirred at room temperature for 5 min and then a solution of ((R)-3-amino-2-hydroxy-propyl)-cyclohexylmethyl-phosphinic acid benzyl ester hydrochloride (2.589 g, 7.15 mmol) in DMF (15 mL) was added via cannula. Triethylamine (2.0 mL, 14.3 mmol) was added dropwise to the reaction mixture and the resulting solution was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate (75 mL) and was washed with saturated NaHCO3, half saturated brine and then brine. The organic layer was dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by SiO2 chromatography using 0-5% MeOH/CH2Cl2 as the eluent to yield the title diastereomeric compound (2.254 g, 4.296 mmol). 1H NMR (CD3OD, 300 MHz): δ 7.43-7.30 (m, 5H), 5.03 (m, 2H), 4.07 (m, 1H), 3.83-3.80 (m, 1H), 3.34-3.23 (m, 2H), 2.07-1.94 (m, 3H), 1.91-1.75 (m, 5H), 1.69-1.60 (m, 3H), 1.43 (s, 9H), 1.28-1.17 (m, 3H), 1.07-1.00 (m, 2H), 0.94 (d, J=6.6 Hz, 3H), 0.90 (d, J=6.6 Hz, 3H). 31P NMR (CD3OD, 300 MHz): δ 61.20, 60.48. LCMS m/z: [M+H]+=525.3.

Source