Benzaldehyde → 2,3-Diphenyl-3-hydroxymethyl-1-methyl piperidine

HRID 569242Notes

Reaction equation

HRID 569242 reaction equation
[C:1]1([CH:7]2[CH2:13][CH2:12][C:11](=O)[O:10][C:8]2=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:15](=O)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[CH3:23][NH2:24].B#B.[BH4-].[Na+].Cl>C1(C)C(C)=CC=CC=1.C1COCC1.COCCOCCOC.B(F)(F)F.O>[C:16]1([CH:15]2[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)([CH2:8][OH:10])[CH2:13][CH2:12][CH2:11][N:24]2[CH3:23])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

12

Reactant 6

HCID 240BenzaldehydeHCID 313Hydrochloric AcidHCID 6329MethylamineHCID 962932-Phenylglutaric anhydrideHCID 4311764Sodium borohydrideHCID 6328200Diboron

Product 1

HCID 133620132,3-Diphenyl-3-hydroxymethyl-1-methyl piperidine

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 6356Boron trifluorideSolventHCID 7237O-XyleneSolventHCID 8028TetrahydrofuranSolventHCID 8150DiglymeSolvent2×

Procedure

8.3 g (0.0436 mole) of 2-phenylglutaric anhydride and 5.2 g (0.0436 mole) of Schiff base, prepared from benzaldehyde and methylamine, are refluxed at 140° in 50 ml of xylene for 12 hr. After cooling the solid is collected and washed with xylene and ether: 7.6 g of 2,3-diphenyl-1-methyl-piperidin-6-one-3-carboxylic acid, mp 268°-72° (diastereomeric mixture). A solution of 7.3 g (0.0263 mole) of the above compound in 10 ml of THF is treated with diborane generated from 7.5 g of NaBH4 in 150 ml of diglyme and 50.6 ml of BF3 -etherate in 150 ml of diglyme. After completion of the reaction 30 ml of 6N HCl are added very slowly at first. 100 ml of water are added and the THF removed in vacuo. The water solution is adjusted to pH 8-9 with 6N NaOH and extracted with methylenechloride. The gummy residue (6.3 g) is crystallized from ether: 4.2 g (62%) of title compound mp 138°-44° (very likely diastereomeric mixture).

Workup

  1. temperatureAfter cooling the solid
  2. customis collected
  3. washwashed with xylene and ether
  4. additionare added very slowly at first
  5. customthe THF removed in vacuo
  6. extractionextracted with methylenechloride
  7. customThe gummy residue (6.3 g) is crystallized from ether

Sources & evidence

ORD record
ord-fd53e6069a2540aa95654aa843e2731d
Source dataset
uspto-grants-1988_03
Patent number
US04731457

Reaction notes

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