Methane, dichloromethoxy- → HCID 10397697, compound

HRID 637728Notes

Reaction equation

HRID 637728 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[O:11][CH2:10][CH2:9][CH2:8][C:7]=2[CH:12]=1.Cl[CH:14]([O:16][CH3:17])Cl>C(Cl)Cl.[Ti](Cl)(Cl)(Cl)Cl>[CH3:1][O:2][C:3]1[C:12]([CH:14]=[O:16])=[C:7]2[CH2:8][CH2:9][CH2:10][O:11][C:6]2=[CH:5][CH:4]=1.[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:14]=[O:16])[C:6]2[O:11][CH2:10][CH2:9][CH2:8][C:7]=2[CH:12]=1.[CH3:17][O:16][C:14]1[C:4]([CH:3]=[O:2])=[CH:5][C:6]2[O:11][CH2:10][CH2:9][CH2:8][C:7]=2[CH:12]=1

Participants

7

Reactant 2

HCID 21004Methane, dichloromethoxy-HCID 113786796-Methoxychroman

Product 3

HCID 7116255HCID 7116255, compoundYield 20.4%HCID 10352557HCID 10352557, compoundYield 20.2%HCID 10397697HCID 10397697, compoundYield 20.9%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of 6-methoxy-3,4-dihydrobenzopyran (133.0 g, 811 mmol) in dry methylene chloride (1850 mL) was cooled to 5° under nitrogen and titanium tetrachloride (145 mL, 250.2 g, 1319 mmol) was added dropwise over 15 minutes. Upon completion of this addition dichloromethylmethylether (60 mL, 76.26 g, 663 mmol) was added dropwise over 45 minutes. A slight exotherm was observed during the addition (reaction temperature=16°). The cooling bath was removed and the mixture allowed to stir for three hours, then quenched by the dropwise addition of water (300 mL). The resulting mixture was poured into water (1000 mL), the layers separated, and the organic layer washed with water (1000 mL). The combined aqueous layers were back extracted with methylene chloride (500 mL), then the combined organic extracts were washed with brine (2×1000 mL), dried (Na2SO4) and concentrated to a dark oil (152.0 g). Purification by preparative HPLC (Waters Prep 500, 9:1 hexane:ethylacetate as eluant) afforded, in order of elution, 6-methoxy-3,4-dihydrobenzopyran-5-carboxaldehyde (32.52 g, 20.9%) m.p. 52°-54°, 6-methoxy-3,4-dihydrobenzopyran-8-carboxaldehyde (31.83 g, 20.4%) m.p. 69°-71°, and 6-methoxy-3,4-dihydrobenzopyran-7-carboxaldehyde (31.49 g, 20.2%) m.p. 57°-59°.

Workup

  1. additionwas added dropwise over 45 minutes
  2. additionA slight exotherm was observed during the addition (reaction temperature=16°)
  3. customThe cooling bath was removed
  4. customquenched by the dropwise addition of water (300 mL)
  5. additionThe resulting mixture was poured into water (1000 mL)
  6. customthe layers separated
  7. washthe organic layer washed with water (1000 mL)
  8. extractionThe combined aqueous layers were back extracted with methylene chloride (500 mL)
  9. washthe combined organic extracts were washed with brine (2×1000 mL)
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated to a dark oil (152.0 g)
  12. customPurification by preparative HPLC (Waters Prep 500, 9:1 hexane:ethylacetate as eluant)

Sources & evidence

ORD record
ord-a83b6cfc0611463e8ac04ff790726bfd
Source dataset
uspto-grants-1985_12
Patent number
US04558067

Reaction notes

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