Methylamine → HCID 15942617, compound

HRID 902325Notes

Reaction equation

HRID 902325 reaction equation
CC1C=CC(S(O[CH2:12][C@H:13]2[CH:22]=[CH: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: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])[CH:22]=[CH:21]2

Participants

5

Reactant 3

HCID 6329MethylamineHCID 14798Sodium HydroxideHCID 86609102HCID 86609102, compound

Product 1

HCID 15942617HCID 15942617, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of [(2R)-8-(2,6-dichlorophenyl)-2H-chromen-2-yl]methyl 4-methylbenzenesulfonate, prepared in Example 35, step 7 (0.33 g, 0.715 mmol) in anhydrous dimethyl sulfoxide (1.2 mL) was added a solution of methylamine (2.0 M in tetrahydrofuran, 3.58 mL, 7.15 mmol) and the mixture heated at 60° C. in a sealed vial for 26 hours. The cooled reaction mixture was then poured into 1:1 v/v 2.0 M aqueous sodium hydroxide solution:saturated brine (50 mL) and the product extracted with ethyl acetate (50 mL). The separated organic extract was washed with 1:1 v/v 2.0 M aqueous sodium hydroxide solution:saturated brine (50 mL), and half 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 160 mg (70%) of {[(2R)-8-(2,6-dichlorophenyl)-2H-chromen-2-yl]methyl}methylamine as a yellow syrup. The product was dissolved 2-propanol (1.5 mL) and diethyl ether (3 mL) and a solution of hydrogen chloride (1.0 M in diethyl ether, 0.36 mL, 0.36 mmol) was added followed by hexane (4 mL). The resulting white precipitate was filtered to afford 121 mg (47%) of {[(2R)-8-(2.6-dichlorophenyl)-2H-chromen-2-yl]methyl}methylamine hydrochloride as a tan solid. HRMS: calcd for C17H15Cl2NO+H+, 320.06034. found (ESI, [M+H]+), 320.0619.

Workup

  1. customThe cooled reaction mixture
  2. extractionsaturated brine (50 mL) and the product extracted with ethyl acetate (50 mL)
  3. extractionThe separated organic extract
  4. washwas washed with 1:1 v/v 2.0 M aqueous sodium hydroxide solution
  5. dry with materialsaturated brine (50 mL), and half saturated brine (50 mL), dried 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-d3a0bf7622f640faa8b90de7b9962d98
Source dataset
uspto-grants-2008_04
Patent number
US07365095B2

Reaction notes

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