Triethylamine → racemic methyl 2-(3,4-dichlorophenyl)-2-methyl-2H-chromene-3-carboxylate

HRID 409515Notes

Reaction equation

HRID 409515 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([CH3:24])[CH:18]([C:19]([O:21][CH3:22])=[O:20])[CH:17](O)[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[O:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].C(N(CC)CC)C.CS(Cl)(=O)=O.N12CCCN=C1CCCCC2>ClCCl.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([CH3:24])[C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:17][C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[O:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 67155870Methyl 2-(3,4-dichlorophenyl)-4-hydroxy-2-methylchroman-3-carboxylate

Product 1

HCID 67155803racemic methyl 2-(3,4-dichlorophenyl)-2-methyl-2H-chromene-3-carboxylateYield 46.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of crude methyl 2-(3,4-dichlorophenyl)-4-hydroxy-2-methylchroman-3-carboxylate (100 mg, 272 μmol) in dichloromethane (2.0 mL) was stirred on an ice bath and treated with triethylamine (76 μL, 545 μmol), then dropwise with methanesulfonyl chloride (23 μL, 300 μmol). After stirring for 1.5 h, the solution was warmed to rt. After stirring at rt for 6 h, the solution was diluted with dichloromethane, washed with 1.0 M aqueous HCl, dried over sodium sulfate and concentrated under vacuum. The resulting residue was dissolved in benzene (2.0 mL), treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (55 μL, 408 μmol) and stirred at rt for 25 min. After this time, the resulting mixture was heated to 60° C. where it stirred for 5.25 h. After this time, the solution was cooled to rt, diluted with ethyl acetate, washed with water, 1.0 M aqueous HCl, saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride, dried over sodium sulfate and then concentrated under vacuum to yield a residue. The residue was purified by rotary TLC (silica gel, 92:8 hexane-ethyl acetate) to provide racemic methyl 2-(3,4-dichlorophenyl)-2-methyl-2H-chromene-3-carboxylate as a colorless gum (44 mg, 46%). 1H NMR (400 MHz, CDCl3) δ ppm 2.02 (s, 3 H) 3.73 (s, 3 H) 6.82 (d, J=8.1 Hz, 1 H) 6.92 (dt, J=7.6, 1.0 Hz, 1 H) 7.15 (dd, J=7.6, 1.5 Hz, 1 H) 7.25 (dt, J=7.9, 1.5 Hz, 1 H) 7.37 (m, 2 H) 7.58 (s, 1 H) 7.61 (t, J=1.5 Hz, 1 H).

Workup

  1. stirringAfter stirring at rt for 6 h
  2. washwashed with 1.0 M aqueous HCl
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under vacuum
  5. dissolutionThe resulting residue was dissolved in benzene (2.0 mL)
  6. stirringstirred at rt for 25 min
  7. temperatureAfter this time, the resulting mixture was heated to 60° C. where it
  8. stirringstirred for 5.25 h
  9. temperatureAfter this time, the solution was cooled to rt
  10. washwashed with water, 1.0 M aqueous HCl, saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride
  11. dry with materialdried over sodium sulfate
  12. concentrationconcentrated under vacuum
  13. customto yield a residue
  14. customThe residue was purified by rotary TLC (silica gel, 92:8 hexane-ethyl acetate)

Sources & evidence

ORD record
ord-75c6b7eeec2c4712b24f2ef8c9147d79
Source dataset
uspto-grants-2014_06
Patent number
US08759390B2

Reaction notes

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