(S)-1-(2-Fluorophenyl)ethylamine → HCID 178462013, compound

HRID 339892

Reaction equation

HRID 339892 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@@H:8]([NH2:10])[CH3:9].Br[C:12]1[CH:13]=[C:14]([C:18]2([CH3:31])[C:23]([CH3:25])([CH3:24])[O:22][C:21](OCC)=[N:20][S:19]2(=[O:30])=[O:29])[CH:15]=[CH:16][CH:17]=1>ClCCl.C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@@H:8]([NH:10][C:21]1[O:22][C:23]([CH3:25])([CH3:24])[C:18]([CH3:31])([C:14]2[CH:15]=[CH:16][CH:17]=[CH:12][CH:13]=2)[S:19](=[O:30])(=[O:29])[N:20]=1)[CH3:9]

Participants

5

Reactant 2

HCID 7023579(S)-1-(2-Fluorophenyl)ethylamineHCID 683592355-(3-Bromophenyl)-2-ethoxy-5,6,6-trimethyl-5,6-dihydro-1,4,3-oxathiazine 4,4-dioxide

Product 1

HCID 178462013HCID 178462013, compoundYield 47.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

In a round-bottom flask, 92 mg of 5-(3-bromophenyl)-2-ethoxy-5,6,6-trimethyl-5,6-dihydro-1,4,3-oxathiazine 4,4-dioxide stereomer 1 were dissolved in 1.3 ml of dichloromethane and admixed with 45 mg of (S)-1-(2-fluorophenyl)ethylamine. After stirring at room temperature and under a gentle argon stream for 18 hours, the conversion was checked by LCMS. Since it was incomplete, the reaction mixture was taken up in 1.5 ml of THF and stirred at 50° C. for 5 hours. After the removal of the solvent under reduced pressure, the oily residue was stirred at 95° C. for 2 hours and then at room temperature for 48 hours. According to LCMS, the reaction remained incomplete. The residue was dissolved under inert gas in 2 ml of ethanol and, with addition of 50 mg of 10% Pd/C, stirred under a hydrogen atmosphere at room temperature for 16 hours. After the addition of a further 50 mg of 10% Pd/C, the reaction mixture was stirred under the same conditions for a further 24 hours. After filtration to remove solid constituents, the filtrate was concentrated by rotary evaporation and the residue was purified in a purification laboratory by means of preparative HPLC. The product-containing fractions were combined, the acetonitrile was removed under reduced pressure, and the aqueous residue was lyophilized. This gave the product (45.7 mg) with a molecular weight of 390.5 g/mol (C20H23FN2O3S); MS (ESI): m/e=391 (M+H+).

Workup

  1. stirringstirred at 50° C. for 5 hours
  2. customAfter the removal of the solvent under reduced pressure
  3. stirringthe oily residue was stirred at 95° C. for 2 hours
  4. waitat room temperature for 48 hours
  5. dissolutionThe residue was dissolved under inert gas in 2 ml of ethanol and, with addition of 50 mg of 10% Pd/C
  6. stirringstirred under a hydrogen atmosphere at room temperature for 16 hours
  7. additionAfter the addition of a further 50 mg of 10% Pd/C
  8. stirringthe reaction mixture was stirred under the same conditions for a further 24 hours
  9. filtrationAfter filtration
  10. customto remove solid constituents
  11. concentrationthe filtrate was concentrated by rotary evaporation
  12. customthe residue was purified in a purification laboratory by means of preparative HPLC
  13. customthe acetonitrile was removed under reduced pressure

Sources & evidence

ORD record
ord-bc8de94e3a8b42c48397dab37f5701b3
Source dataset
uspto-grants-2014_11
Patent number
US08895547B2

Linked notes

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