Triethylamine → N-methoxyethoxyacetyl-(L)-valine tert-butyl ester

HRID 1291776

Reaction equation

HRID 1291776 reaction equation
C(N(CC)CC)C.[C:8]([O:12][C:13](=[O:19])[C@H:14]([CH:16]([CH3:18])[CH3:17])[NH2:15])([CH3:11])([CH3:10])[CH3:9].[CH3:20][O:21][CH2:22][CH2:23][O:24][CH2:25][C:26](O)=[O:27].C(OP(C#N)(=O)OCC)C>CN(C=O)C.C(Cl)Cl>[C:8]([O:12][C:13](=[O:19])[C@H:14]([CH:16]([CH3:17])[CH3:18])[NH:15][C:26](=[O:27])[CH2:25][O:24][CH2:23][CH2:22][O:21][CH3:20])([CH3:11])([CH3:10])[CH3:9]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 27642(2-Methoxyethoxy)acetic acidHCID 76257Diethyl cyanophosphonateHCID 114626tert-Butyl L-valinate

Product 1

HCID 80707032N-methoxyethoxyacetyl-(L)-valine tert-butyl esterYield 81.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

At 0°, 6.4 ml (45.7 mmol) of triethylamine are added to a solution of 5 g (23.9 mmol) of (L)-valine tert-butyl ester, 2.91 g (21.7 mmol) of 2-(methoxyethoxy)-acetic acid and 3.55 g (21.7 mmol) of cyanophosphonic acid diethyl ester in 30 ml of DMF and the mixture is then stirred overnight at RT. The reaction mixture is diluted with methylene chloride, washed in succession with 10% citric acid, saturated sodium hydrogen carbonate solution and saturated sodium chloride solution and, after concentration by evaporation of the organic phase, yields 5.1 g of N-methoxyethoxyacetyl-(L)-valine tert-butyl ester, which is stirred for 1 h at RT in 22 ml of a (1:1) mixture of methylene chloride and TFA. Concentration by evaporation of the reaction solution yields the title compound in the form of a colourless oil. 1H-NMR (200 MHz, CDCl3): 10.0 (s, broad, 1H), 7.62 d, broad, 1H), 4.55 (m, 1H), 4.10 (s, 2H), 3.70 (m, 2H), 3.58 (m, 2H), 3.40 (s, 3H), 2.28 (m, 1H), 0.98 (d, J=7 Hz, 3H), 0.95 (d, J=7 Hz, 3H).

Workup

  1. washwashed in succession with 10% citric acid, saturated sodium hydrogen carbonate solution and saturated sodium chloride solution
  2. concentrationafter concentration
  3. customby evaporation of the organic phase

Sources & evidence

ORD record
ord-6319baa8aaeb4eb9aab4cda2aff0c823
Source dataset
uspto-grants-1998_05
Patent number
US05753652

Linked notes

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