Triethylamine → (6S)-1-(2-chloro-3-(trifluoromethyl)benzyl)-6-ethylpiperazine-2,3-dione

HRID 576698Notes

Reaction equation

HRID 576698 reaction equation
Cl.[NH2:2][C@@H:3]([CH2:12][CH3:13])[CH2:4][NH:5][C:6](=[O:11])[C:7]([O:9]C)=O.[Cl:14][C:15]1[C:22]([C:23]([F:26])([F:25])[F:24])=[CH:21][CH:20]=[CH:19][C:16]=1[CH:17]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(N(CC)CC)C>C(Cl)Cl.Cl>[Cl:14][C:15]1[C:22]([C:23]([F:24])([F:25])[F:26])=[CH:21][CH:20]=[CH:19][C:16]=1[CH2:17][N:2]1[C@@H:3]([CH2:12][CH3:13])[CH2:4][NH:5][C:6](=[O:11])[C:7]1=[O:9]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 27366722-Chloro-3-(trifluoromethyl)benzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 90402534(S)-methyl 2-((2-aminobutyl)amino)-2-oxoacetate hydrochloride

Product 1

HCID 90402241(6S)-1-(2-chloro-3-(trifluoromethyl)benzyl)-6-ethylpiperazine-2,3-dioneYield 38%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolvent

Procedure

To an ice cold solution of (S)-methyl 2-((2-aminobutyl)amino)-2-oxoacetate hydrochloride (967 mg, 4.6 mmol) and 2-chloro-3-trifluoromethylbenzaldehyde (957 mg, 4.6 mmol) in DCM (26 mL) was added sodium triacetoxyborohydride (1.46 g, 6.9 mmol). The resulting mixture was allowed to warm to rt and stirred for 13 h. Triethylamine (1.9 mL) was added, and after 2 h the reaction was diluted with 1M HCl. The organic layer was washed with sat. aq. NaHCO3 and brine, then dried (Na2SO4), and concentrated to afford a clear oil. Purification by chromatography (SiO2; hexanes—10% IPA/EtOAc) provided the desired product as a white solid (580 mg, 38%). MS (ESI): mass calcd. for C14H14ClF3N2O2, 334.1; m/z found, 335.1 [M+H]+. 1H NMR (500 MHz, CDCl3) δ 8.10 (d, J=4.5 Hz, 1H), 7.68 (dd, J=7.8, 1.1 Hz, 1H), 7.62 (d, J=7.7 Hz, 1H), 7.39 (t, J=7.8 Hz, 1H), 5.28 (d, J=15.5 Hz, 1H), 4.48 (d, J=15.5 Hz, 1H), 3.70 (dd, J=13.4, 4.2 Hz, 1H), 3.44 (ddd, J=13.4, 5.5, 1.6 Hz, 1H), 3.37-3.28 (m, 1H), 1.25-1.17 (m, 2H), 0.99 (t, J=7.5 Hz, 3H).

Workup

  1. washThe organic layer was washed with sat. aq. NaHCO3 and brine
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. customto afford a clear oil
  5. customPurification by chromatography (SiO2; hexanes—10% IPA/EtOAc)

Sources & evidence

ORD record
ord-1f0a50ea59bf4383a7ab8713bdf791c3
Source dataset
uspto-grants-2015_05
Patent number
US09040534B2

Reaction notes

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