Trifluoroacetic acid → O-benzyl L-seryl L-valyl glycyl glycine methyl ester trifluoroacetate

HRID 2370908Notes

Reaction equation

HRID 2370908 reaction equation
COC(=O)CN[C:6](=[O:43])[CH2:7][NH:8][C:9](=[O:42])[C@H:10](C(C)C)[NH:11][C:12](=[O:38])[C@H:13]([CH:35]([CH3:37])[CH3:36])[NH:14][C:15](=[O:34])[C@H:16]([CH2:25][O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[NH:17]C(OC(C)(C)C)=O.[C:45]([OH:51])([C:47]([F:50])([F:49])[F:48])=[O:46]>C(Cl)Cl>[F:48][C:47]([F:50])([F:49])[C:45]([OH:51])=[O:46].[CH3:45][O:46][C:6](=[O:43])[CH2:7][NH:8][C:9](=[O:42])[CH2:10][NH:11][C:12](=[O:38])[C@H:13]([CH:35]([CH3:36])[CH3:37])[NH:14][C:15](=[O:34])[C@H:16]([CH2:25][O:26][CH2:27][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)[NH2:17]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 86671365Boc-Ser(Bn)-Val-Val-Gly-Gly-OMe

Product 1

HCID 86762378O-benzyl L-seryl L-valyl glycyl glycine methyl ester trifluoroacetateYield 92%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-tert-butoxycarbonyl O-benzyl L-seryl L-valyl L-valyl glycyl glycine methyl ester 24 (SEQ ID NO: 7) (0.525 g, 0.844 mmol) was dissolved in a 50% (v/v) solution of TFA in CH2Cl2 (12 mL) at room temperature. The reaction mixture was stirred for 1 h 30 min before the solvent and bulk of excess TFA were evaporated. Et2O (10 mL) was added to the liquid residue, which resulted in precipitation of a white solid. The Et2O was decanted off and the residue washed with additional portions of Et2O (2×10 mL) and dried under reduced pressure overnight affording the title compound as a white solid (0.494 g, 92%); δH (300 MHz; d6-DMSO) 8.47 (1H, d, J 9, NH(Valx)), 8.29-8.20 (5H, m, NH3+/NH(Glyx)/NH(Glyy)), 8.00 (1H, d, J 8, NH(Valy)) 7.38-7.27 (5H, m, Ph), 4.51 (2H, s, CH2Ph), 4.34 (1H, dd, J 7 and 9, CαH(Valx)), 4.17-4.12 (2H, m, CαH(Valy)/CαH(Ser(Bn))), 3.85 (2H, dd, J 4 and 6, CαH2(Glyx)), 3.76-3.64 (4H, m, CH2(Ser(Bn))/CαH2(Glyy)), 3.62 (3H, s, OCH3), 2.04-1.89 (2H, m, CH(CH3)2), 0.89-0.81 (12H, m, CH3); δC (75 MHz; d6-DMSO) 171.1, 170.6, 170.1, 169.2, 166.2, 158.3 (q, JCF 32) 137.5, 128.2, 127.6, 127.5, 116.9 (q, JCF 291), 72.5, 68.6, 58.1, 57.9, 52.2, 51.6, 41.6, 40.5, 30.6, 30.2, 19.1, 19.1, 18.2, 18.0; m/z (ESI) 522.2920 (M+; C25H40N5O7 requires 522.2927)

Workup

  1. customwere evaporated
  2. additionEt2O (10 mL) was added to the liquid residue, which
  3. customresulted in precipitation of a white solid
  4. customThe Et2O was decanted off
  5. washthe residue washed with additional portions of Et2O (2×10 mL)
  6. customdried under reduced pressure overnight

Sources & evidence

ORD record
ord-df0753da453b482285c0a4d553e4cb8c
Source dataset
uspto-grants-2014_04
Patent number
US08710008B2

Reaction notes

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