Methanol → HCID 58017418, compound

HRID 451986Notes

Reaction equation

HRID 451986 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][CH:22]=1)[C:5]([C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:8]1)=[O:6].C1(C)C=CC=CC=1.CO>C1COCC1.CCOC(C)=O>[OH:6][C@H:5]([C:4]1[CH:3]=[C:2]([CH3:1])[CH:22]=[CH:21][CH:20]=1)[C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13]([O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:14])[CH2:8]1

Participants

6

Reactant 3

HCID 887MethanolHCID 1140TolueneHCID 58017384HCID 58017384, compound

Product 1

HCID 58017418HCID 58017418, compoundYield 11.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-15 °C

Procedure

To a solution of (R)-tert-butyl 3-(3-methylbenzoyl)piperidine-1-carboxylate (168 g, 0.55 mol) in anhydrous THF (600 mL) at −15° C. under nitrogen was added dropwise a solution of 1 M R-CBS-oxazaborolidine in toluene (82 mL, 82 mmol, 0.15 eq). After stirring for 1 hr at −15° C., a solution of 10 M BH3 in THF (60 mL, 0.60 mol, 1.1 eq) was added dropwise. After addition, the reaction mixture was stirred for 2 hr at −15° C. TLC indicated the starting material was disappeared. Methanol (400 mL) was added dropwise carefully at −15° C. The solvent was removed under reduced pressure, the residue was purified by column chromatography on silica gel eluting with EtOAc/hexane (1:30→1:15) to provide the light yellow oil (95 g, HPLC≧70%, ratio≧3:1). The mixture was dissolved in EtOAc until the alcohol was just dissolved (about 5 mL/1 g), the solvent was removed on the rotary evaporator until a few crystals appeared. The solution was cooled to rt slowly and stood for 1-2 hr. To the above solution was added hexane (about 300 mL) and then filtered, the crystals were washed with cool hexane and re-crystallized two more times to afford the pure isomer (R)-tert-butyl 3-((S)-hydroxy(m-tolyl)methyl)piperidine-1-carboxylate (20 g, ee≧99%).

Workup

  1. additionAfter addition
  2. stirringthe reaction mixture was stirred for 2 hr at −15° C
  3. customThe solvent was removed under reduced pressure
  4. customthe residue was purified by column chromatography on silica gel eluting with EtOAc/hexane (1:30→1:15)
  5. customto provide the light yellow oil (95 g, HPLC≧70%, ratio≧3:1)
  6. dissolutionwas just dissolved (about 5 mL/1 g)
  7. customthe solvent was removed on the rotary evaporator until a few crystals
  8. temperatureThe solution was cooled to rt slowly
  9. waitstood for 1-2 hr
  10. additionTo the above solution was added hexane (about 300 mL)
  11. filtrationfiltered
  12. washthe crystals were washed with cool hexane
  13. customre-crystallized two more times

Sources & evidence

ORD record
ord-07ec999de9dc4d49bf492d63c87df48a
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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