Methylamine → HCID 15942185, compound

HRID 902294Notes

Reaction equation

HRID 902294 reaction equation
CC1C=CC(S(O[CH2:12][C@H:13]2[CH2:22][CH2:21][C:20]3[C:15](=[C:16]([C:23]4[CH:28]=[C:27]([Cl:29])[CH:26]=[CH:25][C:24]=4[Cl:30])[CH:17]=[CH:18][CH:19]=3)[O:14]2)(=O)=O)=CC=1.[CH3:31][NH2:32]>CS(C)=O.C(OCC)C>[Cl:30][C:24]1[CH:25]=[CH:26][C:27]([Cl:29])=[CH:28][C:23]=1[C:16]1[CH:17]=[CH:18][CH:19]=[C:20]2[C:15]=1[O:14][C@@H:13]([CH2:12][NH:32][CH3:31])[CH2:22][CH2:21]2

Participants

5

Reactant 2

HCID 6329MethylamineHCID 86609098HCID 86609098, compound

Product 1

HCID 15942185HCID 15942185, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
60 °C

Procedure

To a suspension of [(2R)-8-(2,5-dichlorophenyl)-3,4-dihydro-2H-chromen-2-yl]methyl 4-methylbenzenesulfonate (0.15 g, 0.324 mmol) in dimethylsulfoxide (0.5 mL) was added a solution of methylamine (2.0 M in tetrahydrofuran, 1.62 mL, 3.24 mmol) and the mixture heated to 60° C. in a sealed vial for 24 hours. The cooled reaction mixture was then diluted with diethyl ether (10 mL), washed with 1.0 M aqueous sodium hydroxide solution (5 mL) and water (5×5 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure to afford a yellow oil. Purification by flash chromatography using a solvent gradient of 0.5 to 5% ammonia saturated methanol solution in dichloromethane gave {[(2R)-8-(2,5-dichlorophenyl)-3,4-dihydro-2H-chromen-2-yl]methyl}methylamine as a colorless syrup. The product was dissolved in diethyl ether (1 mL) and a solution of hydrogen chloride (1.0 M in diethyl ether, 0.25 mL, 0.25 mmol) was added followed by 2-propanol (3 drops). The resulting white precipitate was filtered and the solid product triturated with diethyl ether (3×3 mL) to afford 56 mg (48%) of {[(2R)-8-(2,5-dichlorophenyl)-3,4-dihydro-2H-chromen-2-yl]methyl}methylamine hydrochloride as a white solid. MS (ESI) m/z 322.0 ([M+H]+).

Workup

  1. customThe cooled reaction mixture
  2. washwashed with 1.0 M aqueous sodium hydroxide solution (5 mL) and water (5×5 mL)
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto afford a yellow oil
  7. customPurification by flash chromatography

Sources & evidence

ORD record
ord-cbffbcf406ec4a2091d7ba05fdbc6e32
Source dataset
uspto-grants-2008_04
Patent number
US07365095B2

Reaction notes

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