Hydrochloric Acid → (2S,3S,5R)-2-(3,4-difluorophenyl)-3,5-dimethylmorpholine hydrochloride

HRID 962905Notes

Reaction equation

HRID 962905 reaction equation
OS(O)(=O)=O.[F:6][C:7]1[CH:8]=[C:9]([C@@H:14]([OH:22])[C@@H:15]([NH:17][C@H:18]([CH3:21])[CH2:19]O)[CH3:16])[CH:10]=[CH:11][C:12]=1[F:13].[ClH:23]>ClCCl.C(OCC)C>[ClH:23].[F:6][C:7]1[CH:8]=[C:9]([C@@H:14]2[O:22][CH2:19][C@@H:18]([CH3:21])[NH:17][C@H:15]2[CH3:16])[CH:10]=[CH:11][C:12]=1[F:13]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 1118Sulfuric AcidHCID 54225803(1R,2S)-1-(3,4-difluorophenyl)-2-[[(1R)-2-hydroxy-1-methylethyl]amino]propanol

Product 1

HCID 67706283(2S,3S,5R)-2-(3,4-difluorophenyl)-3,5-dimethylmorpholine hydrochlorideYield 49.8%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

To concentrated H2SO4 (100 ml) was added a solution of (1R, 2S)-1-(3,4-difluorophenyl)-2-[[(1R)-2-hydroxy-1-methylethyl]amino]propanol (17.1 g, 0.07 mole) in dichloromethane (100 ml). The reaction was worked up as in Example 1 to yield the crude reaction product as the free base. The crude product was dissolved in diethyl ether and treated with ethereal hydrogen chloride. The hydrochloride salt was recrystallized from ethanol-diethyl ether mixtures to give 9.2 g (49.8% of theory) of (2S, 3S, 5R)-2-(3,4-difluorophenyl)-3,5-dimethylmorpholine hydrochloride as a white solid. m.p. 318° C. [α]20D =+24.6° (c=0.710, 95% ethanol).

Workup

  1. customto yield the crude
  2. customreaction product as the free base
  3. customThe hydrochloride salt was recrystallized from ethanol-diethyl ether mixtures

Sources & evidence

ORD record
ord-dc6d19f018c343efb2eb8f0380a6f690
Source dataset
uspto-grants-1998_06
Patent number
US05760224

Reaction notes

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