1,2-Dichloroethane → tert-Butyl (3-trifluoromethylbenzoyl)glycine

HRID 270228Notes

Reaction equation

HRID 270228 reaction equation
Cl.[C:2]([NH:6][CH2:7][C:8]([OH:10])=[O:9])([CH3:5])([CH3:4])[CH3:3].[F:11][C:12]([F:23])([F:22])[C:13]1[CH:14]=[C:15]([CH:19]=[CH:20][CH:21]=1)[C:16](O)=[O:17].C(N(CC)C(C)C)(C)C.C(Cl)CCl>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:2]([N:6]([C:16](=[O:17])[C:15]1[CH:19]=[CH:20][CH:21]=[C:13]([C:12]([F:11])([F:22])[F:23])[CH:14]=1)[CH2:7][C:8]([OH:10])=[O:9])([CH3:5])([CH3:4])[CH3:3]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 99633-(Trifluoromethyl)benzoic acidHCID 81531DiisopropylethylamineHCID 17748195N-tert-Butylglycine hydrochloride

Product 1

HCID 79262260tert-Butyl (3-trifluoromethylbenzoyl)glycine

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

tert-Butyl glycine hydrochloride (6.6 g, 50 mmol) was suspended in methylene chloride and meta-trifluoromethyl benzoic acid (9.5 g, 50 mmol) was added, followed by N,N-diisopropylethylamine (17.5 mL, 100 mmol), EDC (10.2 g, 53 mmol), and DMAP (300 mg, 2.5 mmol). The reaction was stirred for 12 hrs at RT and partitioned between EtOAc and 1 N HCl. The organic phase was washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. The material was purified via flash chromatography to give tert-Butyl (3-trifluoromethylbenzoyl)glycine as a clear and colorless oil (12 g), which was dissolved in methylene chloride (40 mL), cooled to 0° C., and treated with trifluoroacetic acid (20 mL). The reaction was stirred for 3.5 hrs at RT and concentrated in vacuo. The material was redissolved in methylene chloride and concentrated again; this procedure was repeated three more times to give the desired carboxylic acid 1.2 (Z=—C(O)—, R2=3-trifluoromethylphenyl, all other R=H, 8.9 g). 1H-NMR (300 MHz): δ 8.03 (s, 1H), 7.94 (d, 1H, J=7.7 Hz), 7.66 (d, 1H, J=7.7 Hz), 7.48 (t, 1H, J=7.9 Hz), 4.08 (s, 2H).

Workup

  1. custompartitioned between EtOAc and 1 N HCl
  2. washThe organic phase was washed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe material was purified via flash chromatography

Sources & evidence

ORD record
ord-1e63ad097a39464daf0b1d6871381f62
Source dataset
uspto-grants-2008_11
Patent number
US07449493B2

Reaction notes

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