(+)-N-Methylephedrine → HCID 22005089, compound

HRID 324890Notes

Reaction equation

HRID 324890 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:24]([C:41](=[O:43])[CH3:42])=[C:25]([C:34]2[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=2)[C:26]([CH2:32][CH3:33])=[C:27]([CH:29]([CH3:31])[CH3:30])[CH:28]=1)([CH3:22])[CH3:21]>C(OCC)C>[CH:20]([C:23]1[C:24]([CH:41]([OH:43])[CH3:42])=[C:25]([C:34]2[CH:35]=[CH:36][C:37]([F:40])=[CH:38][CH:39]=2)[C:26]([CH2:32][CH3:33])=[C:27]([CH:29]([CH3:31])[CH3:30])[CH:28]=1)([CH3:21])[CH3:22]

Participants

5

Reactant 3

HCID 102023(+)-N-MethylephedrineHCID 21226445Aluminium lithium hydrideHCID 22005134HCID 22005134, compound

Product 1

HCID 22005089HCID 22005089, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

To a solution of (1S,2R)-(+)-N-methylephedrine (6.29 g, 35.1 mol) in diethyl ether (45 mL) was added lithium aluminum hydride (1M/diethyl ether, 1.5 eq., 35 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 J (6.64 g, 20.3 mmol) was dissolved in 60 mL of dry diethyl ether 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 2.0 hours and then allowed to warm overnight. The reaction was quenched at 0° C. with water (30 mL) and diluted with diethyl ether (250 mL), washed with water (3×200 mL), brine (100 mL) and dried with MgSO4 Filtration and concentration afford a residue which was filtered through a pad of silica (400 g, 80% dichloromethane/hexane) to give the titled compound (99% e.e.) as a white solid (5.85 g, 17.8 mmol, 88%). mp 143-145° C.; Rf=0.1 (50% CH2Cl2/hexane); 1H NMR (300 MHz, CDCl3): δ 7.34 (s, 1H), 7.15 (m, 4H), 4.68 (dq, J=3.3, 7 Hz, 1H), 3.88 (septet, J=7 Hz, 1H), 3.18 (septet, J=7 Hz, 1H), 2.29 (q, J=7.7 Hz, 2H), 1.68 (s, 1H), 1.37 (d, J=4.8 Hz, 3H), 1.26 (m, 12H), 0.890 (t, J=7.4 Hz, 3H); FAB-MS calcd for (C22H29FO) 328, found 328 (M+); Anal. Calcd for C22H29FO: C, 80.45; H, 8.90; F, 5.78. Found: C, 80.19; H, 8.77; F, 5.84; [α]22=+26.6.

Workup

  1. temperatureThe reaction was refluxed for 1.5 h.
  2. custom−78° C
  3. customrise above −60° C.
  4. temperatureto warm overnight
  5. customThe reaction was quenched at 0° C. with water (30 mL)
  6. additiondiluted with diethyl ether (250 mL)
  7. washwashed with water (3×200 mL), brine (100 mL)
  8. dry with materialdried with MgSO4 Filtration and concentration
  9. customafford a residue which
  10. filtrationwas filtered through a pad of silica (400 g, 80% dichloromethane/hexane)

Sources & evidence

ORD record
ord-cc355fccb1d4426395f70577a91c9b4b
Source dataset
uspto-grants-2001_04
Patent number
US06218431B1

Reaction notes

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