Reaktion #159338

Reaktionsgleichung

((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

Ausbeute 60.1%

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

Ausbeute 60.1%

Lösungsmittel

ethyl acetate

DMF

DMF

Reaktionsbedingungen

Aufarbeitung

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

Vorschrift

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.

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