Hydrochloric Acid → 3-[5-Chloromethyl-3,3-dimethyl-2,3-dihydro-benzofuran-7-yl)-4-trifluoromethoxy-benzaldehyde

HRID 460301Notes

Reaction equation

HRID 460301 reaction equation
O[CH2:2][C:3]1[CH:4]=[C:5]([C:14]2[CH:15]=[C:16]([CH:19]=[CH:20][C:21]=2[O:22][C:23]([F:26])([F:25])[F:24])[CH:17]=[O:18])[C:6]2[O:10][CH2:9][C:8]([CH3:12])([CH3:11])[C:7]=2[CH:13]=1.[ClH:27]>C1(C)C=CC=CC=1>[Cl:27][CH2:2][C:3]1[CH:4]=[C:5]([C:14]2[CH:15]=[C:16]([CH:19]=[CH:20][C:21]=2[O:22][C:23]([F:26])([F:25])[F:24])[CH:17]=[O:18])[C:6]2[O:10][CH2:9][C:8]([CH3:12])([CH3:11])[C:7]=2[CH:13]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 184454093-(5-Hydroxymethyl-3,3-dimethyl-2,3-dihydro-benzofuran-7-yl)-4-trifluoromethoxy-benzaldehyde

Product 1

HCID 184454063-[5-Chloromethyl-3,3-dimethyl-2,3-dihydro-benzofuran-7-yl)-4-trifluoromethoxy-benzaldehyde

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 3-(5-hydroxymethyl-3,3-dimethyl-2,3-dihydro-benzofuran-7-yl)-4-trifluoromethoxy-benzaldehyde (1.25 g, 3.41 mmol) (example 10c) and 12N HCl (8.5 mL) in toluene (35 mL) was heated at reflux for 1 hour. The solution was cooled to room temperature and the layers were separated. The aqueous layer was extracted twice with ethyl acetate. The organic combined extract was washed with water, brine, dried (MgSO4), filtered and evaporated. To the residue obtained (3-[5-chloromethyl-3,3-dimethyl-2,3-dihydro-benzofuran-7-yl)-4-trifluoromethoxy-benzaldehyde) (example 10e), diluted in dimethylformamide (35 mL), were added potassium carbonate (3.49 g, 25.25 mmol) then dimethylamine hydrochloride (1.47 g, 18.04 mmol). The mixture was stirred at room temperature for 3 hours. Water was added and the layers separated. The mixture was extracted with ethyl acetate and the organic combined extract was washed with water, brine, dried (MgSO4), filtered and evaporated. The residue was chromatographed on silica gel (10% methanol in dichloromethane) to afford 742 mg of 3-(5-Dimethylaminomethyl-3,3-dimethyl-2,3-dihydro-benzofuran-7-yl)-4-trifluoromethoxy-benzaldehyde. 56% yield. 1H-NMR (300 MHz, CDCl3): 1.38 (s, 6H), 2.30 (s, 6H), 3.47 (s, 2H), 4.25 (s, 2H), 7.06 (s, 1H), 7.16 (s, 1H), 7.48 (d, J=8.5 Hz, 1H), 7.90 (dd, J1=8.5 Hz, J2=2.1 Hz, 1H), 8.03 (d, J=2.1 Hz, 1H), 10.03 (s, 1H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 1 hour
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted twice with ethyl acetate
  5. extractionThe organic combined extract
  6. washwas washed with water, brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customevaporated

Sources & evidence

ORD record
ord-2bed92e3bd73417880c83ce234c99c63
Source dataset
uspto-grants-2007_03
Patent number
US07196108B2

Reaction notes

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