Dichloromethane → HCID 58481132, compound

HRID 1625691Notes

Reaction equation

HRID 1625691 reaction equation
Cl.[NH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C@H:7]([NH:12][C:13](=[O:18])[C:14]([F:17])([F:16])[F:15])[C:8]([O:10][CH3:11])=[O:9].C(N(CC)C(C)C)(C)C.ClCCl.[CH2:31]=[C:32]1[O:36][C:34](=[O:35])[CH2:33]1>C(OCC)(=O)C>[CH3:11][O:10][C:8](=[O:9])[C@@H:7]([NH:12][C:13](=[O:18])[C:14]([F:16])([F:17])[F:15])[CH2:6][CH2:5][CH2:4][CH2:3][NH:2][C:34](=[O:35])[CH2:33][C:32](=[O:36])[CH3:31]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 12661DiketeneHCID 81531DiisopropylethylamineHCID 86658641HCID 86658641, compound

Product 1

HCID 58481132HCID 58481132, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To (S)-methyl 6-amino-2-(2,2,2-trifluoroacetamido)hexanoate hydrochloride (0.943 g, 3.22 mmol), N,N-diisopropyl ethylamine (DIEA, 1.39 mL) and dichloromethane (DCM, 10 mL) in a 40 mL glass vial was added diketene (0.37 mL) under N2 atmosphere, and the reaction was stirred at ambient temperature for 16 hours. The reaction mixture was diluted with ethyl acetate (EtOA), washed successively with H2O, 1 N HCl, H2O, sat aq Na2CO3, and sat aq NaCl, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by a SiO2 flash chromatography, affording (S)-methyl-6-(3-oxobutanamido)-2-(2,2,2-trifluoroacetamido)hexanoate (TU3000-012) as a yellow oil. MS (ESI+): calcd. 341.12. found 341.10 (MH+). H-NMR (400 MHz, CDCl3):1.33 (2H, m), 1.55 (2H, m), 1.89 (2H, m), 2.259(3H, s), 3.31 (2H, m), 3.410 (2H, s), 3.783 (3H, s), 4.543 (1H, dt, J=4.4, 8.0 Hz). 7.091 (1H, br.s), 7.279 (1H, br.d, J=7.6 Hz). F-NMR (376 MHz, CDCl3): −75.609.

Workup

  1. washwashed successively with H2O, 1 N HCl, H2O
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by a SiO2 flash chromatography

Sources & evidence

ORD record
ord-5a1e908fcc2c4eedb0f6021ff91c7c51
Source dataset
uspto-grants-2014_07
Patent number
US08785151B2

Reaction notes

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