Formic Acid → (R)-tert-Butyl (3-hydroxy-3-phenylpropyl)carbamate

Et3N (2.0 mL, 14.35 mmol) and HCOOH (0.4 mL, 10.60 mmol) were added to a solution of (R)-3-(3-((tert-butoxycarbonyl)amino)-1-hydroxypropyl)phenyl trifluoromethanesulfonate (1.05 g, 2.63 mmol) and Ar was bubbled through the mixture for one minute. 1,3-Bis(diphenylphosphino)propane (1,3-dppp) (0.080 g, 0.194 mmol) and Pd(OAc)2 (0.050 g, 0.223 mmol) were added to the reaction mixture and the later was degassed by applying vacuum/Ar cycle three times. The reaction mixture was heated at +60° C. for 5 h and concentrated under reduced pressure. Aqueous NH4Cl (25%) was added to the residue and the mixture was extracted with MTBE twice. Combined organic layers were washed with brine and concentrated under reduced pressure. Purification by flash chromatography (10%-50% EtOAc-hexanes gradient) gave (R)-tert-butyl (3-hydroxy-3-phenylpropyl)carbamate as a colorless oil. Yield (0.64 g, 97%); 1H NMR (400 MHz, DMSO-d6) δ 7.22-7.30 (m, 4H), 7.14-7.21 (m, 1H), 6.72 (br. t, 1H), 5.14 (d, J=4.4 Hz, 1H), 4.51 (dd, J=6.5, 10.9 Hz, 1H), 2.87-2.98 (m, 2H), 1.60-1.70 (m, 2H), 1.33 (s, 9H).

1. customwas bubbled through the mixture for one minute
2. customthe later was degassed
3. temperatureThe reaction mixture was heated at +60° C. for 5 h
4. concentrationconcentrated under reduced pressure
5. additionAqueous NH4Cl (25%) was added to the residue
6. extractionthe mixture was extracted with MTBE twice
7. washCombined organic layers were washed with brine
8. concentrationconcentrated under reduced pressure
9. customPurification by flash chromatography (10%-50% EtOAc-hexanes gradient)

ORD record

ord-a97edc1ffac540258ed2e2c534dd3aca

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09133154B2