Trifluoroacetic acid → HCID 87403310, compound

HRID 588921Notes

Reaction equation

HRID 588921 reaction equation
[CH3:1][O:2][C:3](=[O:36])[C:4]([CH3:35])([CH3:34])[NH:5][C:6](=[O:33])[C@H:7]([CH2:28][O:29][C:30]#[C:31][CH3:32])[NH:8][C:9](=[O:27])[C:10]([CH3:26])([CH3:25])[NH:11][C:12](=[O:24])[C:13]([CH3:23])([CH3:22])[NH:14]C(OC(C)(C)C)=O.[C:37]([OH:43])([C:39]([F:42])([F:41])[F:40])=[O:38]>C(Cl)Cl>[F:40][C:39]([F:42])([F:41])[C:37]([OH:43])=[O:38].[CH3:1][O:2][C:3](=[O:36])[C:4]([CH3:35])([CH3:34])[NH:5][C:6](=[O:33])[C@H:7]([CH2:28][O:29][C:30]#[C:31][CH3:32])[NH:8][C:9](=[O:27])[C:10]([CH3:26])([CH3:25])[NH:11][C:12](=[O:24])[C:13]([CH3:22])([CH3:23])[NH2:14]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 87402917HCID 87402917, compound

Product 1

HCID 87403310HCID 87403310, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-tert-butoxycarbonyl α,α-dimethylglycyl α,α-dimethylglycyl O-propynyl-L-seryl α,α-dimethylglycine methyl ester 16 (4.79 g, 9.35 mmol) was dissolved in 50% (v/v) TFA in CH2Cl2 (70 mL) and the reaction mixture stirred for 1 h 30 min at room temperature. The solvent and bulk of excess TFA were evaporated and CH2Cl2 (2×70 mL) added and evaporated. The residue was washed with Et2O (3×35 mL), redissolved in CH2Cl2 (100 mL), the solvent evaporated and the residue washed with Et2O (70 mL). Finally, CH2Cl2 (3×120 mL) was added and evaporated and the residue dried under high vacuum affording a white solid (4.93 g, 100%); 1H NMR (200 MHz, DMSO-d6) δ 8.38-8.00 (m, 5H, NH3+/NH(Aib2)/NH(Aib4)), 7.25 (d, J=7.8 Hz, 1H, NH(propSer)), 4.33 (q, J=5.4 Hz, 1H, CαH), 4.11 (d, J=2.4 Hz, 2H, CH2CCH), 3.62 (d, J=5.4 Hz, 2H, CH2), 3.54 (s, 3H, OCH3), 3.43 (t, J=2.3 Hz, 1H, CCH), 1.49 (s, 6H, CH3), 1.40 (s, 6H, CH3), 1.35 (s, 6H, CH3); 13C NMR (75 MHz, DMSO-d6) δ 174.2, 173.2, 171.3, 168.6, 158.4 (q, JCF=32 Hz), 117.1 (q, J=297 Hz), 80.1, 77.3, 69.0, 57.7, 56.7, 56.6, 55.1, 52.4, 51.9, 25.0, 24.8, 24.7, 24.6, 23.3, 23.3; HRMS (m/z): M+ calcd. for C19H33N4O6, 413.2400. found, 413.2391; Anal. Calcd. for C21H33F3N4O8: C, 47.91; H, 6.32; N, 10.64. Found: C, 47.2; H, 6.2; N, 10.5.

Workup

  1. customThe solvent and bulk of excess TFA were evaporated
  2. additionCH2Cl2 (2×70 mL) added
  3. customevaporated
  4. washThe residue was washed with Et2O (3×35 mL)
  5. dissolutionredissolved in CH2Cl2 (100 mL)
  6. customthe solvent evaporated
  7. washthe residue washed with Et2O (70 mL)
  8. additionFinally, CH2Cl2 (3×120 mL) was added
  9. customevaporated
  10. customthe residue dried under high vacuum

Sources & evidence

ORD record
ord-ddc4d590db694b64b17c39476a285e2e
Source dataset
uspto-grants-2016_01
Patent number
US09227995B2

Reaction notes

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