Allyl bromide → (S)-3-(Allyloxy)-2-((tert-butoxycarbonyl)amino)propanoic acid

HRID 2370888Notes

Reaction equation

HRID 2370888 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:12]([OH:14])=[O:13])[CH2:10][OH:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH2:17](Br)[CH:18]=[CH2:19]>CN(C=O)C>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:12]([OH:14])=[O:13])[CH2:10][O:11][CH2:19][CH:18]=[CH2:17])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 7841Allyl bromideHCID 24758Sodium hydrideHCID 98766N-[tert-butoxycarbonyl]-L-serine

Product 1

HCID 11032134(S)-3-(Allyloxy)-2-((tert-butoxycarbonyl)amino)propanoic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

N-tert-butoxycarbonyl L-serine (27.04 g, 0.1318 mol) was dissolved in DMF (220 mL). The solution was cooled to 0° C. (icebath) before sodium hydride (60% dispersion in mineral oil, 11.59 g, 0.2898 mol) was added slowly under stirring. After gas evolution had ceased allyl bromide (17.54 g, 0.1450 mol) was added dropwise and the reaction mixture stirred for 18 hours at room temperature. The solvent was evaporated and the residue dissolved in H2O (500 mL). The solution was washed with Et2O (2×250 mL), cooled to 0° C. (icebath) and acidified to pH 2.5 by addition of 2M aqueous H2SO4. The resulting solution/suspension was extracted with EtOAc (5×250 mL). The combined organic extracts were dried with anhydrous MgSO4 and the solvent evaporated overnight affording the title compound as a slightly yellow-orange viscous liquid (26.86 g, 83%) with spectral characteristics in accordance with published data;3,4 δH (200 MHz; d6-DMSO) 12.52 (1H, br s, COOH), 6.84 (1H, d, J 8, NH), 5.81 (1H, ddt, J 5, 10 and 17, CH═CH2), 5.20 (1H, ddd, J 1, 3 and 17, CH═CHH), 5.09 (1H, ddd, J 1, 3 and 10, CH═CHH), 4.10 (1H, dt, J 5 and 8, CαH), 3.96-3.92 (2H, dt, J 1 and 5, CH2CH═CH2), 3.56 (2H, d, J 5, CH2), 1.34 (9H, s, (CH3)3); δC (75 MHz; d6-DMSO) 171.9, 155.3, 134.8, 116.5, 78.1, 71.0, 69.1, 53.7, 28.1; m/z (ESI) 268.0 ([M+Na]+)

Workup

  1. additionwas added slowly
  2. additionwas added dropwise
  3. stirringthe reaction mixture stirred for 18 hours at room temperature
  4. customThe solvent was evaporated
  5. dissolutionthe residue dissolved in H2O (500 mL)
  6. washThe solution was washed with Et2O (2×250 mL)
  7. additionacidified to pH 2.5 by addition of 2M aqueous H2SO4
  8. extractionThe resulting solution/suspension was extracted with EtOAc (5×250 mL)
  9. dry with materialThe combined organic extracts were dried with anhydrous MgSO4
  10. customthe solvent evaporated overnight

Sources & evidence

ORD record
ord-68620306d5cd4b23aa58d31526ae6bca
Source dataset
uspto-grants-2014_04
Patent number
US08710008B2

Reaction notes

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