p-Toluenesulfonic acid → 4-(3-Bromo-4,5-dimethoxyphenyl)-7-dimethylamino-2-methoxy-chroman

HRID 1454000Notes

Reaction equation

HRID 1454000 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:12]2[C:21]3[C:16](=[CH:17][C:18]([N:22]([CH3:24])[CH3:23])=[CH:19][CH:20]=3)[O:15][CH:14](N3CCOCC3)[CH2:13]2)[CH:5]=[C:6]([O:10][CH3:11])[C:7]=1[O:8][CH3:9].C1(C)C=CC(S(O)(=O)=O)=CC=1.[C:42](Cl)(=[O:44])C.C(=O)(O)[O-].[Na+]>CO>[Br:1][C:2]1[CH:3]=[C:4]([CH:12]2[C:21]3[C:16](=[CH:17][C:18]([N:22]([CH3:23])[CH3:24])=[CH:19][CH:20]=3)[O:15][CH:14]([O:44][CH3:42])[CH2:13]2)[CH:5]=[C:6]([O:10][CH3:11])[C:7]=1[O:8][CH3:9]

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 6367Acetyl chloride2×HCID 516892Sodium BicarbonateHCID 69005398[4-(3-Bromo-4,5-dimethoxyphenyl)-2-morpholin-4-yl-chroman-7-yl]-dimethyl-amine

Product 1

HCID 100023204-(3-Bromo-4,5-dimethoxyphenyl)-7-dimethylamino-2-methoxy-chromanYield 51%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of [4-(3-bromo-4,5-dimethoxyphenyl)-2-morpholin-4-yl-chroman-7-yl]-dimethyl-amine (10 mg; 0.021 mmol) and p-toluene sulphonic acid (8 mg) in methanol (1 ml) was stirred overnight at room temperature. The mixture was cooled to 0° C. Acetyl chloride (10 μl) was added and the reaction was stirred at room temperature for 0.5 h. TLC showed formation of product. Another 10 μl of acetyl chloride was added at 0° C., and the mixture was stirred for 0.5 h at room temperature. It was neutralized with saturated sodium bicarbonate and extracted with dichloromethane. The extract was washed with saturated sodium chloride solution, dried and evaporated. The title compound was obtained by passing the crude product through a bond-elute (hexane:ethyl acetate=9:1 as eluent) (yield: 51%). 1H NMR (acetone-d6): 7.00, 6.99, 6.97 and 6.93 (d each, J=1.8 Hz; 2H), 6.54 (t, J=9.6 Hz; 1H), 6.28-6.31 (two doublets overlapped, J=8.5 Hz; fine splitting J=2.2 Hz; 1H), 6.22-6.23 (two doublets, J=3.3 Hz; 1H), 5.18 (t, J=2.5 Hz) and 5.12 (dd, J=2.4, 7.8 Hz) (1H), 4.08-4.15 (m, 1H), 3.87, 3.84, 3.80 and 3.79, (s each, 6H), 3.53 and 3.47 (s each, 3H), 2.91 and 2.90 (s each, 6H), 2.29-2.35 (m) and 1.98-2.19 (m, overlapping with acetone signal) (2H).

Workup

  1. temperatureThe mixture was cooled to 0° C
  2. stirringthe reaction was stirred at room temperature for 0.5 h
  3. stirringthe mixture was stirred for 0.5 h at room temperature
  4. extractionextracted with dichloromethane
  5. washThe extract was washed with saturated sodium chloride solution
  6. customdried
  7. customevaporated

Sources & evidence

ORD record
ord-76b9740a9b69476b94c20348cc7aa0e1
Source dataset
uspto-grants-2009_01
Patent number
US07476741B2

Reaction notes

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