Chloroform → L-valyl L-valine methyl ester trifluoroacetate

HRID 2370892Notes

Reaction equation

HRID 2370892 reaction equation
[CH3:1][O:2][C:3](=[O:23])[C@H:4]([CH:20]([CH3:22])[CH3:21])[NH:5][C:6](=[O:19])[C@H:7]([CH:16]([CH3:18])[CH3:17])[NH:8]C(OC(C)(C)C)=O.[C:24]([OH:30])([C:26]([F:29])([F:28])[F:27])=[O:25].C(Cl)(Cl)Cl>C(Cl)Cl>[F:27][C:26]([F:29])([F:28])[C:24]([OH:30])=[O:25].[CH3:1][O:2][C:3](=[O:23])[C@H:4]([CH:20]([CH3:22])[CH3:21])[NH:5][C:6](=[O:19])[C@H:7]([CH:16]([CH3:17])[CH3:18])[NH2:8]

Participants

5

Reactant 3

HCID 6212ChloroformHCID 6422Trifluoroacetic acid2×HCID 13386190N-boc-l-valyl-l-valine methyl ester

Product 1

HCID 86671346L-valyl L-valine methyl ester trifluoroacetateYield 97%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-tert-butoxycarbonyl L-valyl L-valine methyl ester (4) (10.07 g, 30.48 mmol, 1.00 eq.) was treated with a 50% (v/v) TFA solution in CH2Cl2 for 2 hours at room temperature. The solvent and bulk of excess TFA were evaporated affording a clear, crystalline solid which contained TFA as judged by 1H-NMR. Small portions of purified CHCl3 (i.e. without EtOH as stabiliser) were added and evaporated under reduced pressure four times resulting in an off-white solid. The solid was washed with Et2O (3×50 mL) and dried under reduced pressure affording a white solid (10.20 g, 97%). The compound has been mentioned in the literature, but spectral data was not provided55; δH (300 MHz; d6-DMSO) 8.62 (1H, d, J 7, NH), 8.17 (3H, br s, NH3+), 4.19 (1H, dd, J 7 and 6, CαH(Val2)), 3.75 (1H, br d, J 5, CαH(Val1)), 3.64 (3H, s, OCH3), 2.16-2.01 (2H, m, CH(CH3)2), 0.96-0.90 (12H, m, CH(CH3)2); δC (75 MHz; d6-DMSO) 171.4, 168.4, 158.4 (q, JCF 31), 117.1 (q, JCF 297) 57.7, 56.9, 51.7, 29.9, 29.6, 18.8, 18.1, 18.1, 17.4; m/z (ESI) 231.1710 (M+; C11H23N2O3 requires 231.1708)

Workup

  1. customThe solvent and bulk of excess TFA were evaporated
  2. customaffording a clear, crystalline solid which
  3. customevaporated under reduced pressure four times
  4. customresulting in an off-white solid
  5. washThe solid was washed with Et2O (3×50 mL)
  6. customdried under reduced pressure

Sources & evidence

ORD record
ord-8440d2ffae35419c8349366d96aa4d57
Source dataset
uspto-grants-2014_04
Patent number
US08710008B2

Reaction notes

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