Pivaloyl chloride → Ethyl 6-chloro-2-fluoro-3-(pivalamidomethyl)benzoate

HRID 59339Notes

Reaction equation

HRID 59339 reaction equation
[NH2:1][CH2:2][C:3]1[C:4]([F:15])=[C:5]([C:11]([Cl:14])=[CH:12][CH:13]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7].[C:16](Cl)(=[O:21])[C:17]([CH3:20])([CH3:19])[CH3:18]>C1COCC1>[Cl:14][C:11]1[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[C:4]([F:15])[C:3]([CH2:2][NH:1][C:16](=[O:21])[C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:13][CH:12]=1

Participants

4

Reactant 2

HCID 62493Pivaloyl chlorideHCID 58483233Ethyl 3-(aminomethyl)-6-chloro-2-fluorobenzoate

Product 1

HCID 58483442Ethyl 6-chloro-2-fluoro-3-(pivalamidomethyl)benzoateYield 63.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 3-(aminomethyl)-6-chloro-2-fluorobenzoate (0.540 g, 2.5 mmol) in THF (5 mL) was added pivaloyl chloride (0.335 g, 2.79 mmol) and TEA (0.1 mL) and the reaction mixture was stirred for 2-3 h at RT. Excess of solvent was removed under vacuum and the residue was diluted with water, extracted with EtOAC and concentrated to afford 0.500 g of the product. 1H NMR (300 MHz, DMSO d6): δ 1.11 (s, 9H), 1.31 (t, J=7.5 Hz, 3H), 4.26 (d, J=5.1 Hz, 2H), 4.39 (q, J=6.6 Hz, 2H), 7.33-7.43 (m, 2H), 8.13 (m, 1H).

Workup

  1. customExcess of solvent was removed under vacuum
  2. additionthe residue was diluted with water
  3. extractionextracted with EtOAC
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-679e0785981e4a348fc8c897ec2e048e
Source dataset
uspto-grants-2016_09
Patent number
US09439890B2

Reaction notes

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