Formaldehyde → 3-[2-Benzyl-6-[(3R,4R)-3-hydroxy-4-methoxypyrrolidin-1-yl]-3-pyridyl]ethynyl-1-methyl-3-piperidinol

HRID 2216373Notes

Reaction equation

HRID 2216373 reaction equation
[CH2:1]([C:8]1[C:13]([C:14]#[C:15][C:16]2([OH:22])[CH2:21][CH2:20][CH2:19][NH:18][CH2:17]2)=[CH:12][CH:11]=[C:10]([N:23]2[CH2:27][C@@H:26]([O:28][CH3:29])[C@H:25]([OH:30])[CH2:24]2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C=O.[C:33](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[CH2:1]([C:8]1[C:13]([C:14]#[C:15][C:16]2([OH:22])[CH2:21][CH2:20][CH2:19][N:18]([CH3:33])[CH2:17]2)=[CH:12][CH:11]=[C:10]([N:23]2[CH2:27][C@@H:26]([O:28][CH3:29])[C@H:25]([OH:30])[CH2:24]2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 98015133-[2-Benzyl-6-[(3R,4R)-3-hydroxy-4-methoxypyrrolidin-1-yl]-3-pyridyl]ethynyl-3-piperidinol

Product 1

HCID 102737293-[2-Benzyl-6-[(3R,4R)-3-hydroxy-4-methoxypyrrolidin-1-yl]-3-pyridyl]ethynyl-1-methyl-3-piperidinolYield 81.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 94.0 mg of 3-[2-Benzyl-6-[(3R,4R)-3-hydroxy-4-methoxypyrrolidin-1-yl]-3-pyridyl]ethynyl-3-piperidinol (Example 1), 34.6 μl of an aqueous solution of 37% formaldehyde and 1.5 ml of dichloromethane was added 73.4 mg of sodium triacetoxyborohydride under ice-cooling, followed by stirring at room temperature for 30 minutes. The organic layer was separated by adding water and ethyl acetate to the reaction mixture, and then it was washed with an aqueous sodium hydrogen carbonate solution and brine, dried over anhydrous magnesium sulfate, and the solvent was removed. The residue was purified by NH-silica gel column chromatography with 5% methanol/ethyl acetate, to give 79.0 mg of the title compound.

Workup

  1. temperaturecooling
  2. customThe organic layer was separated
  3. additionby adding water and ethyl acetate to the reaction mixture
  4. washit was washed with an aqueous sodium hydrogen carbonate solution and brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was removed
  7. customThe residue was purified by NH-silica gel column chromatography with 5% methanol/ethyl acetate

Sources & evidence

ORD record
ord-63d012b9370d4bfc8a38bdf549ded32d
Source dataset
uspto-grants-2006_09
Patent number
US07112593B2

Reaction notes

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