Triethylamine → 4-chloro-N-[4-(2,2-diethoxyethoxy)-3-methoxyphenyl]-2-nitrobenzamide

HRID 1181338

Reaction equation

HRID 1181338 reaction equation
[N+:1]([C:4]1[CH:12]=[C:11]([Cl:13])[CH:10]=[CH:9][C:5]=1[C:6]([OH:8])=O)([O-:3])=[O:2].C(Cl)(=O)C(Cl)=O.[CH2:20]([O:22][CH:23]([O:35][CH2:36][CH3:37])[CH2:24][O:25][C:26]1[CH:32]=[CH:31][C:29]([NH2:30])=[CH:28][C:27]=1[O:33][CH3:34])[CH3:21].C(N(CC)CC)C>C(Cl)Cl.CN(C=O)C.CN(C1C=CN=CC=1)C>[Cl:13][C:11]1[CH:10]=[CH:9][C:5]([C:6]([NH:30][C:29]2[CH:31]=[CH:32][C:26]([O:25][CH2:24][CH:23]([O:35][CH2:36][CH3:37])[O:22][CH2:20][CH3:21])=[C:27]([O:33][CH3:34])[CH:28]=2)=[O:8])=[C:4]([N+:1]([O-:3])=[O:2])[CH:12]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 804754-Chloro-2-nitrobenzoic acidHCID 114367644-(2,2-Diethoxyethoxy)-3-methoxyaniline

Product 1

HCID 113165804-chloro-N-[4-(2,2-diethoxyethoxy)-3-methoxyphenyl]-2-nitrobenzamideYield 86%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-nitro-4-chlorobenzoic acid (5.09, 25.2 mmol) in DCM (100 mL) was added oxalyl chloride (16.8 mL, 34 mmol, 2M in DCM) and DMF (5 drops). The solution was stirred for 1 h and then concentrated by rotary evaporation. The resulting acid chloride was dissolved in DCM. To a solution of 4-(2,2-diethoxyethoxy)-3-methoxyaniline (5.36 g, 21 mmol), triethylamine (4.2 g) and DMAP (0.48 g) in DCM at 0° C. was added the acid chloride solution in 4 portions over 15 min. The reaction was stirred for 18 h and the ice was allowed to melt. The solvents were removed by rotary evaporation and the residue partitioned between water and ethyl acetate. The organic layer was washed with brine, dried and concentrated. The product was purified by by silica gel column chromatography affording the intermediate as a yellow solid (7.91 g, 86%). 1H NMR (DMSO-D6): δ 1.18 (6H, t, J=6.9 Hz), 3.57 (2H, q, J=12.1 Hz), 3.67 (2H, q, J=12.2 Hz), 3.75 (s, 3H), 3.91 (2H, d, J=5.1 Hz), 4.79 (1H, t, J=5.1 Hz), 7.00 (1H, m), 7.18 (1H, d), 7.34 (1H, s), 7.82 (1H, d), 7.95 (1H, d), 8.26 (1H, s), 10.57 (1H, d). LCMS m/z=461 (m+Na+).

Workup

  1. concentrationconcentrated by rotary evaporation
  2. dissolutionThe resulting acid chloride was dissolved in DCM
  3. stirringThe reaction was stirred for 18 h
  4. customThe solvents were removed by rotary evaporation
  5. customthe residue partitioned between water and ethyl acetate
  6. washThe organic layer was washed with brine
  7. customdried
  8. concentrationconcentrated
  9. customThe product was purified by by silica gel column chromatography

Sources & evidence

ORD record
ord-726c8e356584415f80c72854b77112de
Source dataset
uspto-grants-2007_10
Patent number
US07285557B2

Linked notes

Loading…