Dimethylamine, hydrochloride → 4-Amino-3-chloro-N,N-dimethylbenzamide

HRID 84516

Reaction equation

HRID 84516 reaction equation
C[CH2:2][N:3](C(C)C)[CH:4](C)C.Cl.CNC.[NH2:14][C:15]1[CH:23]=[CH:22][C:18]([C:19](O)=[O:20])=[CH:17][C:16]=1[Cl:24].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C1COCC1.CCOC(C)=O>[NH2:14][C:15]1[CH:23]=[CH:22][C:18]([C:19]([N:3]([CH3:4])[CH3:2])=[O:20])=[CH:17][C:16]=1[Cl:24]

Participants

7

Reactant 4

HCID 10473Dimethylamine, hydrochlorideHCID 172114-Amino-3-chlorobenzoic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 202874814-Amino-3-chloro-N,N-dimethylbenzamideYield 100%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

DIPEA (116 mL, 699.5 mmol) was added into a suspension of dimethylamine hydrochloride (28.51 g, 349.6 mmol) in THF (600 mL). The mixture was stirred at room temperature for 0.5 h. Then 4-amino-3-chlorobenzoic acid (30.00 g, 174.8 mmol) and HATU (86.41 g, 227.2 mmol) were added into the above suspension separately. The reaction mixture was continued to be stirred for 1.5 h. Then it was concentrated and the residue was partitioned between EtOAc (300 mL) and water (150 mL). The separated organic phase was washed with water, dried over Na2SO4 and evaporated in vacuum. The crude product was purified by silica gel chromatography, eluted with Hexanes: EtOAc=1:1 to afford 4-amino-3-chloro-N,N-dimethylbenzamide (34.72 g, yield: 89%). ESI-MS: 199.06. 1H NMR (CDCl3, 400 MHz): δ7.39 (s, 1H, ArH), 7.19 (d, J=8.4 Hz, 1H, ArH), 6.74 (d, J=8.4 Hz, 1H, ArH), 4.24 (br, 2H, NH2), 3.05 (s, 6H, 2CH3).

Workup

  1. stirringto be stirred for 1.5 h
  2. concentrationThen it was concentrated
  3. customthe residue was partitioned between EtOAc (300 mL) and water (150 mL)
  4. washThe separated organic phase was washed with water
  5. dry with materialdried over Na2SO4
  6. customevaporated in vacuum
  7. customThe crude product was purified by silica gel chromatography
  8. washeluted with Hexanes

Sources & evidence

ORD record
ord-0c04d74dc3b6421698a8649bd9bf92cf
Source dataset
uspto-grants-2014_09
Patent number
US08846762B2

Linked notes

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