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

HRID 1253410Notes

Reaction equation

HRID 1253410 reaction equation
Br[C:2]([CH3:4])=[CH2:3].[Li]C(C)(C)C.[CH2:10]([O:17][C:18]([NH:20][C@@H:21]([CH2:28][C:29]1[CH:34]=[CH:33][C:32]([CH2:35][NH:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])=[CH:31][CH:30]=1)[C:22](N(OC)C)=[O:23])=[O:19])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.CCOC(C)=O>C1COCC1>[C:40]([O:39][C:37]([NH:36][CH2:35][C:32]1[CH:33]=[CH:34][C:29]([CH2:28][C@H:21]([NH:20][C:18](=[O:19])[O:17][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:22](=[O:23])[C:2]([CH3:4])=[CH2:3])=[CH:30][CH:31]=1)=[O:38])([CH3:43])([CH3:42])[CH3:41]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 112022-BromopropeneHCID 71562122(S)-2-(((Benzyloxy)carbonyl)amino)-3-(4-(((tert-butoxycarbonyl)amino)methyl)phenyl)-N-methoxy-N-methylpropionamideHCID 178418306HCID 178418306, compound

Product 1

HCID 71562123(S)-Benzyl (1-(4-((tert-butyloxycarbonylamino)methyl)phenyl)-4-methyl-3-oxopent-4-en-2-yl)carbamate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

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.

Workup

  1. additionwas added slowly
  2. customconsumption of the Weinreb amide
  3. additionA saturated aqueous NH4Cl solution and EtOAc were added
  4. customthe layers were separated
  5. extractionThe organic layer was extracted with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ce55d4b595df48749162eb2ef11bfbbb
Source dataset
uspto-grants-2013_06
Patent number
US08455431B2

Reaction notes

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