Methylamine → HCID 59701576, compound

HRID 902305Notes

Reaction equation

HRID 902305 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[C:28]([Cl:29])=[CH:27][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].[OH-].[Na+]>CS(C)=O.[Cl-].[Na+].O>[Cl:30][C:24]1[CH:25]=[CH:26][CH:27]=[C:28]([Cl:29])[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

6

Reactant 3

HCID 6329MethylamineHCID 14798Sodium HydroxideHCID 86609104HCID 86609104, compound

Product 1

HCID 59701576HCID 59701576, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of [(2R)-8-(2,6-dichlorophenyl)-3,4-dihydro-2H-chromen-2-yl]methyl 4-methylbenzenesulfonate (239 mg, 0.54 mmol) in anhydrous dimethyl sulfoxide (1 mL) was added a solution of methylamine (2.0 M in tetrahydrofuran, 2.7 mL, 5.4 mmol) and the mixture heated to 60° C. in a sealed vial for 42 hours. The cooled reaction mixture was then poured into 1:1 v/v 2.0 M aqueous sodium hydroxide and saturated brine (50 mL) and the mixture extracted with ethyl acetate (50 mL). The separated organic phase was washed with 1:1 v/v 2.0 M aqueous sodium hydroxide and saturated brine (50 mL), and half saturated brine (50 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure to afford a yellow syrup. Purification by flash chromatography using a solvent gradient of 0.5 to 5% ammonia saturated methanol solution in dichloromethane gave 125 mg (75%) of {[(2R)-8-(2,6-dichlorophenyl)-3,4-dihydro-2H-chromen-2-yl]methyl}methylamine as a white solid. The product was dissolved in 2-propanol (1 mL) and diethyl ether (2.5 mL) and a solution of hydrogen chloride (1.0 M in diethyl ether, 0.39 mL, 0.39 mmol) was added followed by hexane (3 mL). The resulting white precipitate was filtered to afford 118 mg (64%) of {[(2R)-8-(2,6-dichlorophenyl)-3,4-dihydro-2H-chromen-2-yl]methyl}methylamine hydrochloride as a white crystalline solid. HRMS: calcd for C17H17Cl2NO+H+, 322.07599; found (ESI, [M+H]+), 322.0757.

Workup

  1. customThe cooled reaction mixture
  2. extractionthe mixture extracted with ethyl acetate (50 mL)
  3. washThe separated organic phase was washed with 1:1 v/v 2.0 M aqueous sodium hydroxide and saturated brine (50 mL), and half saturated brine (50 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto afford a yellow syrup
  8. customPurification by flash chromatography

Sources & evidence

ORD record
ord-7cb7255d797445b6a3fa0a957018f898
Source dataset
uspto-grants-2008_04
Patent number
US07365095B2

Reaction notes

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