Methanol → HCID 58403627, compound

HRID 1907150Notes

Reaction equation

HRID 1907150 reaction equation
[CH2:1]([C@H:8]([NH:23][C:24](=[O:33])[O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH2:9][NH:10][C:11](=[O:22])[C@H:12]([NH:14]C(OC(C)(C)C)=O)[CH3:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO.C(O)(C(F)(F)F)=O>ClCCl>[NH2:14][C@@H:12]([C:11]([NH:10][CH2:9][C@@H:8]([NH:23][C:24](=[O:33])[O:25][CH2:26][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)[CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:22])[CH3:13]

Participants

5

Reactant 3

HCID 887MethanolHCID 6422Trifluoroacetic acidHCID 68234999HCID 68234999, compound

Product 1

HCID 58403627HCID 58403627, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of benzyl [(1S)-1-benzyl-2-({(2R)-2-[(tert-butoxycarbonyl)amino]propanoyl}amino)ethyl]carbamate (1.43 g, 3.14 mmol) from preparation 1 in dichloromethane (30 mL) and methanol (2 mL) was added TFA (20 ml) at 0° C. The reaction mixture was stirred for 5 hours and then concentrated under reduced pressure. The residue was dissolved in methanol (5 mL) and loaded onto a 20 g SCX2 cartridge (pre-wetted with methanol). The cartridge was eluted with methanol to remove non-basic impurities and then eluted with 3M NH3 in methanol. Fractions containing the title compound were combined and concentrated under reduced pressure to afford the title compound as a white solid in 90% yield, 1.01 g. 1H NMR (400 MHz, MeOH-d4) : 1.21 (d, 3H), 2.70 (dd, 1H), 2.78-2.84 (m, 1H), 3.17 (dd, 1H), 3.31-3.44 (m, 3H), 3.88-4.01 (m, 2H), 4.98 (s, 2H), 7.11-7.34 (m, 10H).

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe residue was dissolved in methanol (5 mL)
  3. washThe cartridge was eluted with methanol
  4. customto remove non-basic impurities
  5. washeluted with 3M NH3 in methanol
  6. additionFractions containing the title compound
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-bd617cd5207b4dbf8588a1dca5988f9c
Source dataset
uspto-grants-2013_12
Patent number
US08598123B2

Reaction notes

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