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

HRID 83860Notes

Reaction equation

HRID 83860 reaction equation
[F: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.CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C1C=CN=CC=1)C>[F: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

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 667406012-(4-Fluoro-3-methoxyphenyl)-2-methylpropanoic acid

Product 1

HCID 866622452-(4-fluoro-3-methoxyphenyl)-N-methoxy-N,2-dimethylpropanamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(4-fluoro-3-methoxyphenyl)-2-methylpropanoic acid (114.75 g, 4.71 mmol) in DCM (2 L) was added N,O-dimethylhydroxylamine hydrochloride (79 g, 0.81 mol), EDCI (145 g, 0.72 mol), DMAP (33 g, 0.27 mol), and DIPEA (471 mL, 2.7 mol). The resulting mixture was stirred 5 h and quenched with H2O (1 L). The organic layer was washed with 1N HCl (1 L×2), satd NaHCO3 (1 L), and brine (1 L) successfully. The organic phase was dried over MgSO4 and concentrated at reduced pressure to afford 2-(4-fluoro-3-methoxyphenyl)-N-methoxy-N,2-dimethylpropanamide as yellow color oil (123 g, 89%). 1H NMR (400 MHz, CDCl3): δ 7.03 (t, 1H), 6.83 (d, 1H), 6.80 (m, 1H), 3.89 (s, 3H), 3.12 (s, 3H), 2.77 (s, 3H), 1.53 (s, 6H).

Workup

  1. customquenched with H2O (1 L)
  2. washThe organic layer was washed with 1N HCl (1 L×2), satd NaHCO3 (1 L), and brine (1 L) successfully
  3. dry with materialThe organic phase was dried over MgSO4
  4. concentrationconcentrated at reduced pressure

Sources & evidence

ORD record
ord-660baeb197cd40388fc44f68da426657
Source dataset
uspto-grants-2014_09
Patent number
US08846739B2

Reaction notes

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