Methylamine → HCID 59701572, compound

HRID 902329Notes

Reaction equation

HRID 902329 reaction equation
CC1C=CC(S(O[CH2:12][CH:13]2[CH:22]=[CH:21][C:20]3[C:15](=[C:16]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=4[Cl:30])[CH:17]=[C:18]([F:23])[CH:19]=3)[O:14]2)(=O)=O)=CC=1.[CH3:31][NH2:32].[OH-].[Na+]>CS(C)=O>[Cl:30][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=1[C:16]1[CH:17]=[C:18]([F:23])[CH:19]=[C:20]2[C:15]=1[O:14][CH:13]([CH2:12][NH:32][CH3:31])[CH:22]=[CH:21]2

Participants

5

Reactant 3

HCID 6329MethylamineHCID 14798Sodium HydroxideHCID 86609118[8-(2-chlorophenyl)-6-fluoro-2H-chromen-2-yl]methyl 4-methylbenzenesulfonate

Product 1

HCID 59701572HCID 59701572, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of [8-(2-chlorophenyl)-6-fluoro-2H-chromen-2-yl]methyl 4-methylbenzenesulfonate (0.33 g, 0.748 mmol) in anhydrous dimethyl sulfoxide (1.2 mL) was added a solution of methylamine (2.0 M in tetrahydrofuran, 3.74 mL, 7.48 mmol) and the mixture heated to 60° C. in a sealed vial for 2 days. The cooled reaction mixture was then poured into 2.0 M aqueous sodium hydroxide solution (40 mL) and the product extracted with ethyl acetate (50 mL). The separated organic extract was washed with water (50 mL), and saturated brine (50 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure to afford a brown syrup. Purification by flash chromatography using a solvent gradient of 0 to 5% ammonia saturated methanol solution in dichloromethane gave 101 mg (45%) of {[8-(2-chlorophenyl)-6-fluoro-2H-chromen-2-yl]methyl}methylamine as a yellow syrup. The product was dissolved 2-propanol (1 mL) and diethyl ether (2 mL), a solution of hydrogen chloride (1.0 M in diethyl ether, 0.33 mL, 0.33 mmol) was added followed by hexane (3 mL). The resulting precipitate was filtered to afford 100 mg (39%) of {[8-(2-chlorophenyl)-6-fluoro-2H-chromen-2-yl]methyl}methylamine hydrochloride as a tan crystalline solid. HRMS: calcd for C17H15ClFNO+H+, 304.08990. found (ESI, [M+H]+), 304.0891.

Workup

  1. customThe cooled reaction mixture
  2. extractionthe product extracted with ethyl acetate (50 mL)
  3. extractionThe separated organic extract
  4. washwas washed with water (50 mL), and saturated brine (50 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto afford a brown syrup
  9. customPurification by flash chromatography

Sources & evidence

ORD record
ord-61a59f4c07f9498f8a8a1103a5f957aa
Source dataset
uspto-grants-2008_04
Patent number
US07365095B2

Reaction notes

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