4-Hydroxybenzaldehyde → (2S,4R,5R)-2-benzhydryl-5-(4-hydroxy-benzylamino)-tetrahydropyran-4-ol

HRID 909760Notes

Reaction equation

HRID 909760 reaction equation
[NH2:1][C@@H:2]1[CH2:7][O:6][C@H:5]([CH:8]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:4][C@H:3]1[OH:21].[OH:22][C:23]1[CH:30]=[CH:29][C:26]([CH:27]=O)=[CH:25][CH:24]=1.C(O)(=O)C.[BH3-]C#N.[Na+].C([O-])(O)=O.[Na+]>ClCCCl.CO.O>[CH:8]([C@@H:5]1[CH2:4][C@@H:3]([OH:21])[C@H:2]([NH:1][CH2:27][C:26]2[CH:29]=[CH:30][C:23]([OH:22])=[CH:24][CH:25]=2)[CH2:7][O:6]1)([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

9

Reactant 5

HCID 1264-HydroxybenzaldehydeHCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 11514718(2S,4R,5R)-5-amino-2-benzhydryl-tetrahydro-pyran-4-ol

Product 1

HCID 11552844(2S,4R,5R)-2-benzhydryl-5-(4-hydroxy-benzylamino)-tetrahydropyran-4-ol

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (2S,4R,5R)-5-amino-2-benzhydryl-tetrahydro-pyran-4-ol 31a (0.02 g, 0.09 mmol), 4-hydroxybenzaldehyde (0.01 g, 0.09 mmol) and glacial acetic acid (0.005 g, 0.09 mmol) in 1,2-dichloroethane (5 ml) was added portionwise NaCNBH3 (0.007 g, 0.11 mmol) in methanol (1 ml). The reaction was continued for 4 hr. Water was added to quench the reaction and the mixture was stirred for 30 minutes at 0° C. The reaction mixture was stirred with saturated aqueous NaHCO3 and the product was extracted with methylene chloride (3×10 ml). The combined organic phases were washed with brine, water and dried over anhydrous Na2SO4. Solvent was removed under reduced pressure, and the residue was purified by flash chromatography (Hexane/Ethyl Acetate/Triethylamine 3:2:0.2) to give (2S,4R,5R)-2-benzhydryl-5-(4-hydroxy-benzylamino)-tetrahydropyran-4-ol, (−)-32a, 0.03 g (80%, [α]D=(−)72.6, c=1, MeOH).

Workup

  1. customto quench
  2. customthe reaction
  3. extractionthe product was extracted with methylene chloride (3×10 ml)
  4. washThe combined organic phases were washed with brine, water
  5. dry with materialdried over anhydrous Na2SO4
  6. customSolvent was removed under reduced pressure
  7. customthe residue was purified by flash chromatography (Hexane/Ethyl Acetate/Triethylamine 3:2:0.2)

Sources & evidence

ORD record
ord-a1b4e615c7c34d3ea96b9e040ef66089
Source dataset
uspto-grants-2011_09
Patent number
US08017791B2

Reaction notes

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