Ethyl Bromide → N-t-butyloxycarbonyl-alpha-ethyl-beta-alanine-t-butyl ester

HRID 361776Notes

Reaction equation

HRID 361776 reaction equation
[C:1]([O:5][C:6](=[O:17])[CH2:7][CH2:8][NH:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])([CH3:4])([CH3:3])[CH3:2].[CH:18]([N-]C(C)C)(C)[CH3:19].[Li+].C(Br)C.[Cl-].[NH4+]>O1CCCC1.CN(P(N(C)C)(N(C)C)=O)C>[C:1]([O:5][C:6](=[O:17])[CH:7]([CH2:18][CH3:19])[CH2:8][NH:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 6332Ethyl BromideHCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamideHCID 540966173-Tert-butoxycarbonylamino-propionic acid tert-butyl ester

Product 1

HCID 86753687N-t-butyloxycarbonyl-alpha-ethyl-beta-alanine-t-butyl esterYield 38.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 12679HexamethylphosphoramideSolvent

Procedure

t-Butyloxycarbonyl-β-alanine t-butyl ester (2.26 g) was added dropwise to a solution of lithium diisopropylamide (LDA) (6.9 ml, 13.8 mmol) in tetrahydrofuran (10 ml) at -78° C. and hexamethylphosphoroamide (HMPA) (2 ml) was added thereto. The temperature of the reaction solution was elevated gradually to -20° C. over 1 hour and lowered again to -78° C. To the reaction solution, ethyl bromide (0.76 ml) was added dropwise. The temperature of the solution was elevated to 0° C. over 2 hours and the reaction was stopped by adding a saturated aqueous solution of ammonium chloride. After the solvent was distilled off, the residue was dissolved in ethyl acetate and washed sequentially with a 5% aqueous solution of sodium hydrogencarbonate, a 5% aqueous solution of citric acid and a saturated aqueous solution of NaCl 3 times each. The ethyl acetate layer was dried over anhydrous sodium sulfate and the solvent was then distilled off to yield an oil. The obtained oil was applied to a silica gel column (2.5×40 cm) and eluted with a mixed solution (hexane:ethyl acetate=40:1). The desired fractions were collected and the solvents were distilled off to yield an oil of N-t-butyloxycarbonyl-α-ethyl-β-alanine-t-butyl ester (0.98 g, 38.9%).

Workup

  1. customlowered again to -78° C
  2. waitThe temperature of the solution was elevated to 0° C. over 2 hours
  3. distillationAfter the solvent was distilled off
  4. dissolutionthe residue was dissolved in ethyl acetate
  5. washwashed sequentially with a 5% aqueous solution of sodium hydrogencarbonate
  6. dry with materialThe ethyl acetate layer was dried over anhydrous sodium sulfate
  7. distillationthe solvent was then distilled off
  8. customto yield an oil
  9. washeluted with a mixed solution (hexane:ethyl acetate=40:1)
  10. customThe desired fractions were collected
  11. distillationthe solvents were distilled off

Sources & evidence

ORD record
ord-d7fb6f41bebe4121a0f4c325340b2c8b
Source dataset
uspto-grants-1999_02
Patent number
US05866592

Reaction notes

Loading…