Acetic Acid → cis-(2-Benzhydryl-tetrahydropyran-4-yl)-(4-fluorobenzyl)-amine

HRID 78892Notes

Reaction equation

HRID 78892 reaction equation
[CH:1]([C@H:14]1[CH2:19][C@@H:18]([NH2:20])[CH2:17][CH2:16][O:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:21][C:22]1[CH:29]=[CH:28][C:25]([CH:26]=O)=[CH:24][CH:23]=1.C(O)(=O)C.[BH3-]C#N.[Na+].C([O-])(O)=O.[Na+]>ClCCCl.CO.O>[CH:1]([C@H:14]1[CH2:19][C@@H:18]([NH:20][CH2:26][C:25]2[CH:28]=[CH:29][C:22]([F:21])=[CH:23][CH:24]=2)[CH2:17][CH2:16][O:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 680234-FluorobenzaldehydeHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 68717496cis-(2-Benzhydryl-tetrahydropyran-4-yl)-amine

Product 1

HCID 66631634cis-(2-Benzhydryl-tetrahydropyran-4-yl)-(4-fluorobenzyl)-amineYield 79.5%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of cis-4-amino-2-diphenylmethylpyran 6a (0.2 g, 0.75 mmol), 4-fluorobenzaldehyde (0.83 g, 0.67 mmol) and glacial acetic acid (0.45 g, 0.75 mmol) in 1,2-dichloroethane (20 ml), was added portion wise NaCNBH3 (0.57 g, 0.9 mmol) dissolved in methanol (5 ml). After 4 hr, water was added to quench the reaction and the mixture was stirred for 30 minutes at 0° C. Then the mixture was made basic with saturated aqueous NaHCO3 and extracted thrice with methylene chloride (3×30 ml). The combined organic phases were washed with brine, water and dried over anhydrous Na2SO4. Solvent was removed in vacuo to collect the crude residue, which was purified by flash chromatography (Hexane/Ethyl Acetate/Triethylamine 3:2:0.2) to give cis-2-diphenylmethyl-4-(4-fluorobenzylamino)-tetrahydropyran 7a (0.20 g, 72.6%) as a liquid.

Workup

  1. customto quench
  2. customthe reaction
  3. extractionextracted thrice with methylene chloride (3×30 ml)
  4. washThe combined organic phases were washed with brine, water
  5. dry with materialdried over anhydrous Na2SO4
  6. customSolvent was removed in vacuo
  7. customto collect the crude residue, which
  8. customwas purified by flash chromatography (Hexane/Ethyl Acetate/Triethylamine 3:2:0.2)

Sources & evidence

ORD record
ord-74c98198118145f0a89d735e610922b9
Source dataset
uspto-grants-2014_09
Patent number
US08841464B2

Reaction notes

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