(2R,3R)-2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol → Bupropion Morpholinol (2R,3R)-Isomer

HRID 650505

Reaction equation

HRID 650505 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@:8]2([OH:17])[O:13][CH2:12][C:11]([CH3:15])([CH3:14])[NH:10][C@@H:9]2[CH3:16])[CH:5]=[CH:6][CH:7]=1>C(OCC)C>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([C@@:8]2([OH:17])[O:13][CH2:12][C:11]([CH3:14])([CH3:15])[NH:10][C@@H:9]2[CH3:16])[CH:5]=[CH:6][CH:7]=1

Participants

3

Reactant 1

HCID 9943908(2R,3R)-2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol

Product 1

HCID 9943907Bupropion Morpholinol (2R,3R)-IsomerYield 90%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

Hydrochloride salts of the separated enantiomers were obtained by the following processes. 1.25 g (0.005 mol) of optical isomer 1 (retention time 6.117 min) ((−)-(2R,3R)-2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol) was dissolved in diethyl ether. The solution was filtered and the filtrate was chilled in an ice-bath adding ethereal hydrogen chloride until the solution was acidic. After standing at ambient temperature for 24h, the resulting solid was filtered, washed with diethyl ether and dried in a vacuum oven at 60° C. for 18h to give 1.32 g (90%) of (−)-(2R,3R)-2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol hydrochloride as a white solid: mp 208-209° C. NMR (300 Mhz, DMSO-d6); δ 9.72 (br, 1H), 8.76 (br, 1H), 7.54-7.41 (m, 5H) 3.98 (d, 1H), 3.52 (d, 1H), 3.37 (br s, 1H), 1.53 (s, 3H), 1.29 (s, 3H), 0.97 (d, 3H). Anal. Calcd for C,13H19Cl2NO2: C, 53.43; H, 6.55; N, 4.79. Found: C, 53.35; H, 6.57; N, 4.71.

Workup

  1. filtrationThe solution was filtered
  2. temperaturethe filtrate was chilled in an ice-bath
  3. additionadding ethereal hydrogen chloride until the solution
  4. customAfter standing at ambient temperature for 24h
  5. filtrationthe resulting solid was filtered
  6. washwashed with diethyl ether
  7. dry with materialdried in a vacuum oven at 60° C. for 18h

Sources & evidence

ORD record
ord-c7b84045abc749f98841b8dc5690e4de
Source dataset
uspto-grants-2001_08
Patent number
US06274579B1

Linked notes

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