Triethylamine → 2-chloro-N-(2,2-dimethoxy-ethyl)-5-nitro-benzamide

HRID 1910770Notes

Reaction equation

HRID 1910770 reaction equation
C(N(CC)CC)C.[CH3:8][O:9][CH:10]([O:13][CH3:14])[CH2:11][NH2:12].[Cl:15][C:16]1[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][C:17]=1[C:18](Cl)=[O:19]>C(Cl)Cl>[Cl:15][C:16]1[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][C:17]=1[C:18]([NH:12][CH2:11][CH:10]([O:13][CH3:14])[O:9][CH3:8])=[O:19]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 89728Aminoacetaldehyde dimethyl acetalHCID 117637Benzoyl chloride, 2-chloro-5-nitro-

Product 1

HCID 612487142-chloro-N-(2,2-dimethoxy-ethyl)-5-nitro-benzamideYield 63.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Thionyl chloride (14 mL, 192 mmol) was added-dropwise to a solution of 2-chloro-5-nitrobenzoic acid (10 g, 49.6 mmol) in chloroform (150 mL) at 0° C. The mixture was heated to reflux for 4 h then cooled to r.t., concentrated in vacuo and dried under high vacuum to yield 2-chloro-5-nitrobenzoyl chloride (10 g, 91.7%) as a solid. Under nitrogen, triethylamine (19 mL, 136 mmol) was added slowly to a solution of aminoacetaldehyde dimethyl acetal (5.43 mL, 50.0 mmol) in dry DCM (20 mL) at 0° C. 2-Chloro-5-nitrobenzoyl chloride (10 g, 45.5 mmol) was slurried in dry DCM (30 mL) and added over a period of 30 minutes. The mixture was allowed to warm to r.t. and stirred overnight then partitioned between water and DCM. The organic phase was washed with saturated sodium bicarbonate solution, water and brine then dried over sodium sulfate and concentrated. The crude product was triturated with petroleum ether then diethyl ether and finally purified by column chromatography on silica gel (60-120 mesh) eluting with ethyl acetate/petroleum ether (2% to 40% gradient) to afford 2-chloro-N-(2,2-dimethoxy-ethyl)-5-nitro benzamide (8.3 g, 63%) as a yellow solid.

Workup

  1. additionadded over a period of 30 minutes
  2. customthen partitioned between water and DCM
  3. washThe organic phase was washed with saturated sodium bicarbonate solution, water and brine
  4. dry with materialthen dried over sodium sulfate
  5. concentrationconcentrated
  6. customThe crude product was triturated with petroleum ether
  7. customdiethyl ether and finally purified by column chromatography on silica gel (60-120 mesh)
  8. washeluting with ethyl acetate/petroleum ether (2% to 40% gradient)

Sources & evidence

ORD record
ord-14f98b44cfb340a7a739a316cab66136
Source dataset
uspto-grants-2013_12
Patent number
US08604029B2

Reaction notes

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