Formaldehyde → (S)-tert-butyl 2-((tert-butyldimethylsilyloxy)methyl)-4-(hydroxymethyl)-5-oxo-5,6-dihydropyridine-1(2H)-carboxylate

HRID 627148Notes

Reaction equation

HRID 627148 reaction equation
[Si:1]([O:8][CH2:9][C@@H:10]1[CH:15]=[C:14]([CH3:16])[C:13](=[O:17])[CH2:12][N:11]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C=O.CC(=O)[O:29]CC>C(Cl)Cl.CO.C(P(CCCC)CCCC)CCC>[Si:1]([O:8][CH2:9][C@@H:10]1[CH:15]=[C:14]([CH2:16][OH:29])[C:13](=[O:17])[CH2:12][N:11]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 712FormaldehydeHCID 8857Ethyl AcetateHCID 89852373tert-Butyl (6S)-6-{[(tert-butyldimethylsilyl)oxy]methyl}-4-methyl-3-oxo-1,2,3,6-tetrahydropyridine-1-carboxylate2×

Product 1

HCID 89852514(S)-tert-butyl 2-((tert-butyldimethylsilyloxy)methyl)-4-(hydroxymethyl)-5-oxo-5,6-dihydropyridine-1(2H)-carboxylateYield 102%

Reagents, catalysts & solvents 3

HCID 13831TributylphosphineCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-tert-butyl 2-((tert-butyldimethylsilyloxy)methyl)-5-oxo-5,6-dihydropyridine-1(2H)-carboxylate (Intermediate 7, 18 g, 52.71 mmol) in a mixture of DCM (900 mL) and MeOH (350 mL) was added successively formaldehyde (42.8 mL, 527.06 mmol) and tributylphosphine (0.692 mL, 3.16 mmol) at rt. The solution was stirred at room temperature for 2-3 hr until TLC (4:1 Hex/EA) showed that the reaction was complete. It was concentrated under reduced pressure and purified by 120 g silica gel column (0-50% Hex/EA) to afford the title compound (20.00 g, 102%) as an oil.

Workup

  1. concentrationIt was concentrated under reduced pressure
  2. custompurified by 120 g silica gel column (0-50% Hex/EA)

Sources & evidence

ORD record
ord-d974857650d74f46af8380d29e833e48
Source dataset
uspto-grants-2016_04
Patent number
US09309245B2

Reaction notes

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