1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-(4-chloro-3-methoxyphenyl)-N-methoxy-N,2-dimethylpropanamide

HRID 1627342Notes

Reaction equation

HRID 1627342 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:13])([CH3:12])[C:9]([OH:11])=O)=[CH:4][C:3]=1[O:14][CH3:15].Cl.[CH3:17][NH:18][O:19][CH3:20].CCN=C=NCCCN(C)C>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:13])([CH3:12])[C:9]([N:18]([O:19][CH3:20])[CH3:17])=[O:11])=[CH:4][C:3]=1[O:14][CH3:15]

Participants

6

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 667403622-(4-Chloro-3-methoxyphenyl)-2-methylpropanoic acid

Product 1

HCID 866622432-(4-chloro-3-methoxyphenyl)-N-methoxy-N,2-dimethylpropanamideYield 96%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(4-chloro-3-methoxyphenyl)-2-methylpropanoic acid (15) (268 g, 1.17 mol) in CH2Cl2 (1.7 L) was added N,O-dimethylhydroxylamine hydrochloride (137 g, 1.4 mol), EDCI (270 g, 1.4 mol), and DMAP (172 g, 1.4 mol). The resulting mixture was stirred for 3 h and washed with 10% citric acid solution (1.5 L), satd NaHCO3 (1.5 L), and brine (1.5 L) successfully. The organic phase was dried over MgSO4, filtered, and concentrated at reduced pressure to afford 2-(4-chloro-3-methoxyphenyl)-N-methoxy-N,2-dimethylpropanamide (16) as a brown solid (276 g, 96%). 1H NMR (400 MHz, CDCl3): δ 7.30-7.32 (d, 1H), 6.81-6.84 (m, 3H), 3.89 (s, 3H), 3.12 (s, 3H), 2.78 (s, 3H), 1.53 (s, 6H).

Workup

  1. washwashed with 10% citric acid solution (1.5 L), satd NaHCO3 (1.5 L), and brine (1.5 L) successfully
  2. dry with materialThe organic phase was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated at reduced pressure

Sources & evidence

ORD record
ord-c9cbd86d7bdd421d9f34f5365dd4f76a
Source dataset
uspto-grants-2014_07
Patent number
US08785488B2

Reaction notes

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