Acetic Acid → Methyl 2-(1-methylpiperidin-4-yl)pyrimidine-5-carboxylate

HRID 1911449Notes

Reaction equation

HRID 1911449 reaction equation
[C:1](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[NH:15]1[CH2:20][CH2:19][CH:18]([C:21]2[N:26]=[CH:25][C:24]([C:27]([O:29][CH3:30])=[O:28])=[CH:23][N:22]=2)[CH2:17][CH2:16]1.C=O.C(O)(=O)C>CO>[CH3:1][N:15]1[CH2:20][CH2:19][CH:18]([C:21]2[N:22]=[CH:23][C:24]([C:27]([O:29][CH3:30])=[O:28])=[CH:25][N:26]=2)[CH2:17][CH2:16]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 66589876HCID 66589876, compound

Product 1

HCID 66589810Methyl 2-(1-methylpiperidin-4-yl)pyrimidine-5-carboxylateYield 94.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

Sodium triacetoxyborohydride (532 mg, 2.51 mmol) was added to methyl 2-(piperidin-4-yl)pyrimidine-5-carboxylate (222 mg, 1.00 mmol), formaldehyde (37% aqueous solution, 1.50 ml, 20.07 mmol) and acetic acid (0.115 ml, 2.01 mmol) in methanol (4.994 ml) at 25° C. The resulting solution was stirred at ambient temperature for 3 days. The reaction mixture was diluted with methanol (20 mL) and the crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH and evaporated to dryness to afford methyl 2-(1-methylpiperidin-4-yl)pyrimidine-5-carboxylate (223 mg, 94%) as a cream waxy solid. This was used directly with no further purification.

Workup

  1. customthe crude product was purified by ion exchange chromatography
  2. washThe desired product was eluted from the column
  3. customevaporated to dryness

Sources & evidence

ORD record
ord-691b79117a1b4da190ee5622f8fa6ba3
Source dataset
uspto-grants-2013_12
Patent number
US08604022B2

Reaction notes

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