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

HRID 460297Notes

Reaction equation

HRID 460297 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 (1.76 g, 4.82 mmol) and 12N HCl (12 mL) in toluene (45 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), diluted in toluene (20 mL), were added ethylene glycol (2.5 mL, 44.34 mmol) and p-toluenesulfonic acid monohydrate (0.44 mmol, 84 mg). The mixture was heated at reflux overnight using a Dean Stark apparatus. The solution was cooled to room temperature, poured into an aqueous solution of sodium bicarbonate, and extracted with ethyl acetate. The organic combined extract was washed with water, brine, dried (MgSO4), filtered and evaporated. The residue was chromatographed on silica gel (50% ethyl acetate in hexane) to afford 830 mg of 2-[7-(5-[1,3]dioxolan-2-yl-2-trifluoromethoxy-phenyl)-3,3-dimethyl-2,3-dihydro-benzofuran-5-ylmethoxy]-ethanol. 38% yield. 1H-NMR (300 MHz, CDCl3): 1.37 (s, 6H), 1.99 (t, J=6.2 Hz, 1H), 3.62 (t, J=4.5 Hz, 2H), 3.78 (m, 2H), 4.02–4.15 (m, 4H), 4.24 (s, 2H), 4.53 (s, 2H), 5.86 (s, 1H), 7.11 (d, J=8.5 Hz, 2H), 7.34 (d, J=8.5 Hz, 1H), 7.49 (d, J=8.5 Hz, 1H), 7.58 (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-5295860496414ea98be280daee5d9207
Source dataset
uspto-grants-2007_03
Patent number
US07196108B2

Reaction notes

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