Reaction #1340592

Reaction equation

Weinreb amide

(S)-2-(((Benzyloxy)carbonyl)amino)-3-(4-(((tert-butoxycarbonyl)amino)methyl)phenyl)-N-methoxy-N-methylpropionamide

EtOAc

2-Bromopropene

tBuLi

→

title compound

(S)-Benzyl (1-(4-((tert-butyloxycarbonylamino)methyl)phenyl)-4-methyl-3-oxopent-4-en-2-yl)carbamate

Solvents

THF

THF

Conditions

Workup

1. 1
   workup.ADDITIONwas added slowly
2. 2
   Otherconsumption of the Weinreb amide
3. 3
   workup.ADDITIONA saturated aqueous NH4Cl solution and EtOAc were added
4. 4
   Otherthe layers were separated
5. 5
   ExtractionThe organic layer was extracted with brine
6. 6
   Dryingdried over MgSO4
7. 7
   Concentrationconcentrated under reduced pressure

Procedure

2-Bromopropene (3.5 eq., 14.0 mmol, 1.25 mL) was dissolved in THF (50 mL) and cooled to −78° C. tBuLi (6.5 eq., 26.0 mmol, 16.3 mL; 1.6 M in hexane) was added slowly and the mixture was stirred for 1 hour at −78° C. after which Weinreb amide 11 (1 eq., 4.0 mmol, 1.89 g) was added in THF (5 mL). The mixture was allowed to warm to −20° C. in 6 hours after which TLC analysis indicated complete consumption of the Weinreb amide. A saturated aqueous NH4Cl solution and EtOAc were added and the layers were separated. The organic layer was extracted with brine, dried over MgSO4 and concentrated under reduced pressure. The title compound was obtained after column chromatography (20%→50% EtOAc/PE) as a colourless oil (yield: 1.71 g, 3.77 mmol, 94%). 1H NMR (400 MHz, CDCl3): δ=7.33-7.24 (m, 5H), 7.11 (d, J=7.87 Hz, 2H), 6.97 (d, J=8.00 Hz, 2H), 6.03 (s, 1H), 5.85 (s, 1H), 5.77 (d, J=8.18 Hz, 1H), 5.30 (dd, J=14.10, 6.11 Hz, 1H), 5.12-5.08 (m, 1H), 5.04 (dd, J=26.54, 12.35 Hz, 2H), 4.21 (d, J=5.41 Hz, 2H), 3.09 (dd, J=13.79, 5.88 Hz, 1H), 2.89 (dd, J=13.76, 5.97 Hz, 1H), 1.84 (s, 3H), 1.44 (s, 9H) ppm. 13C NMR (100 MHz, CDCl3): δ=199.28, 155.66, 155.34, 141.99, 137.40, 136.13, 134.60, 129.27, 128.17, 127.80, 127.71, 126.50, 79.01, 66.45, 55.13, 43.96, 38.76, 28.14, 17.44 ppm. HRMS: calcd. for C26H32N2O5 453.23840 [M+H]+. Found 453.23818.

Source