(+)-N-Methylephedrine → HCID 11186974, compound

HRID 324881Notes

Reaction equation

HRID 324881 reaction equation
C[C@@H](N(C)C)[C@@H](O)C1C=CC=CC=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH:20]([C:23]1[C:28]([C:29](=[O:31])[CH3:30])=[C:27]([C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=2)[C:26]([CH2:39][CH2:40][CH3:41])=[C:25]([CH:42]([CH3:44])[CH3:43])[N:24]=1)([CH3:22])[CH3:21]>CCOCC>[CH:20]([C:23]1[C:28]([CH:29]([OH:31])[CH3:30])=[C:27]([C:32]2[CH:33]=[CH:34][C:35]([F:38])=[CH:36][CH:37]=2)[C:26]([CH2:39][CH2:40][CH3:41])=[C:25]([CH:42]([CH3:43])[CH3:44])[N:24]=1)([CH3:22])[CH3:21]

Participants

5

Reactant 3

HCID 102023(+)-N-MethylephedrineHCID 11371256HCID 11371256, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 11186974HCID 11186974, compoundYield 92,241.398%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

To a solution of (1S,2R)-(+)-N-methylephedrine (31.1 g, 0.174 mol) in ether (208 mL) was added lithium aluminum hydride (1M/diethylether, 1.5 eq., 174 mL) dropwise at 0° C. under argon. The reaction was refluxed for 1.5 h. turning from a clear solution to a white milky solution. The reaction was cooled to room temperature and then −78° C. The intermediate obtained in Step A (39.53g, 0.116 mmol) was dissolved in 400 mL of dry diethyl ether and cooled to 0° C. for a dropwise addition to the reaction mixture (˜2 mL/min., the temperature should not rise above −60° C.). The reaction was kept at −78° C. for 4.0 hours and then allowed to warm overnight. The reaction was quenched at 0° C. with isopropanol (70 mL) and diluted with ether (700 mL), washed with water (4×500 mL), 10% HCl (2×500 mL), brine (2×500 mL) and dried with MgSO4. Filtration and concentration afforded a residue which was filtered through a pad of silica (600 g, 10% diethyl ether/hexane) to give the title compound (97% e.e.) as a white solid (36.67 g, 107 mmol, 92%). 1H NMR (300 MHz, CDCl3): δ 7.11 (m, 4H), 4.67 (dq, J=3.3, 6.6 Hz, 1H), 3.74 (septet, J=6.6 Hz, 1H), 3.20 (septet, J=6.6 Hz, 1H), 2.17 (m, 2 H), 1.61 (d, J=2.9 Hz, 1H), 1.40 (d, J=7.0 Hz, 3H), 1.30 (m, 14H), 0.741 (t, J=7.4 Hz, 3H). FAB-MS: calcd for (C22H30NOF) 343, found 344 (M+H). mp 102-104° C. Rf=0.2 (60% CH2Cl2/hexane).

Workup

  1. temperatureThe reaction was refluxed for 1.5 h.
  2. custom−78° C
  3. temperaturecooled to 0° C. for a dropwise addition to the reaction mixture (˜2 mL/min.
  4. customrise above −60° C.
  5. temperatureto warm overnight
  6. customThe reaction was quenched at 0° C. with isopropanol (70 mL)
  7. additiondiluted with ether (700 mL)
  8. washwashed with water (4×500 mL), 10% HCl (2×500 mL), brine (2×500 mL)
  9. dry with materialdried with MgSO4
  10. filtrationFiltration and concentration
  11. customafforded a residue which
  12. filtrationwas filtered through a pad of silica (600 g, 10% diethyl ether/hexane)

Sources & evidence

ORD record
ord-952320a2f10e4090a4cac05b11a3284e
Source dataset
uspto-grants-2001_04
Patent number
US06218431B1

Reaction notes

Loading…