Diisopropylethylamine → tert-Butyl (3-trifluoromethylbenzoyl)glycine

HRID 488939Notes

Reaction equation

HRID 488939 reaction equation
[N+]([C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:12]=1)[C:7]([OH:9])=O)([O-])=O.C([O:21][C:22](=[O:25])[CH2:23][NH2:24])(C)(C)C.C(N(CC)[CH:30]([CH3:32])[CH3:31])(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=C[C:45]=2N=N1>C(Cl)Cl>[C:30]([N:24]([C:7](=[O:9])[C:6]1[CH:5]=[CH:4][CH:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:10]=1)[CH2:23][C:22]([OH:21])=[O:25])([CH3:32])([CH3:45])[CH3:31]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 151417Glycine tert-butyl esterHCID 6166023-Nitro-5-(trifluoromethyl)benzoic acid

Product 1

HCID 79262260tert-Butyl (3-trifluoromethylbenzoyl)glycine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 3-nitro-5(trifluoromethyl)benzoic acid (7.71 g, 32.8 mmol) and glycine tert-butyl ester (5.23 g, 32.4 mmol) in methylene chloride (330 mL) was charged with N,N-diisopropylethylamine (5.5 mL, 31.8 mmol) and BOP (14.6 g, 32.9 mmol). The reaction was stirred at RT for 14 h, concentrated in vacuo, and diluted with EtOAc (1 L). The organic phase was washed successively with sat. NH4Cl, sat. NaHCO3, and brine before being dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography (SiO2, 50% EtOAc/hexanes) to afford the tert-Butyl (3-trifluoromethylbenzoyl)glycine as an oil. A portion (1.0 g, 2.65 mmol) of this material was dissolved in methylene chloride (8 mL) before being treated with TFA (4 mL). The reaction was stirred for 1 h at RT and then concentrated in vacuo. The residue was dissolved in methlyene chloride and concentrated again; this procedure was repeated twice more to afford the title compound 1.2 (Z=—C(O)—, R2=3-amino-5-(trifluoromethyl)phenyl, all other R=H; 0.77 g) as a white solid. MS found: (M−H)−=291.1.

Workup

  1. concentrationconcentrated in vacuo
  2. additiondiluted with EtOAc (1 L)
  3. washThe organic phase was washed successively with sat. NH4Cl, sat. NaHCO3, and brine
  4. dry with materialbefore being dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography (SiO2, 50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-7d32ddc657994c849bbc7dd31ac81977
Source dataset
uspto-grants-2005_12
Patent number
US06974836B2

Reaction notes

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