1,2-Dichloroethane → 2-Amino-5-fluoro-N-methoxy-N-methylbenzamide

HRID 19675

Reaction equation

HRID 19675 reaction equation
C(N(C(C)C)CC)(C)C.Cl.[CH3:11][O:12][NH:13][CH3:14].[NH2:15][C:16]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:17]=1[C:18](O)=[O:19].C(Cl)CCl>C(Cl)(Cl)Cl.C(Cl)Cl>[NH2:15][C:16]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:17]=1[C:18]([N:13]([O:12][CH3:11])[CH3:14])=[O:19]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 1014122-Amino-5-fluorobenzoic acid

Product 1

HCID 534075722-Amino-5-fluoro-N-methoxy-N-methylbenzamide

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

To a 0° C. mixture of diisopropylethylamine (34.36 mL, 197.25 mmol) and O,N-dimethyl-hydroxylamine hydrochloride (19.24 g, 197.25 mmol) in CHCl3 (300 mL) was added 2-amino-5-fluorobenzoic acid (25.50 g, 164.38 mmol) followed by EDC (31.51 g, 164.38 mmol). The reaction was stirred from 0° C. to ambient temperature over 2 h and then diluted with CH2Cl2 (100 mL), washed with saturated sodium bicarbonate solution (100 mL) and brine (100 mL), dried over Na2SO4, filtered, and concentrated in vacuo. Purification by normal phase chromatography (3-8% MeOH/CH2Cl2) yielded 2-amino-5-fluoro-N-methoxy-N-methylbenzamide as a yellow oil. 1H NMR (CDCl3, 400 MHz) 7.12 (m, 1H, ArH); 6.93 (m, 1H, ArH); 6.65 (m, 1H, ArH); 3.63 (s, 3H, CH3); 3.35 (s, 3H, CH3); MS (Electrospray): m/z 199.1 (M+H).

Workup

  1. washwashed with saturated sodium bicarbonate solution (100 mL) and brine (100 mL)
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification by normal phase chromatography (3-8% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-3d66f49508da4beb9babdb20a9d84317
Source dataset
uspto-grants-2010_06
Patent number
US07745452B2

Linked notes

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