Methanol → 2-hydroxymethyl-3-benzyloxy-6-methyl-pyran-4(1H)-one

HRID 1016683Notes

Reaction equation

HRID 1016683 reaction equation
[OH:1][C:2]1[C:7](=[O:8])[CH:6]=[C:5]([CH3:9])N(C)[C:3]=1[C:11](NC)=[O:12].CC1OC=C(O)C(=[O:19])C=1.[CH2:24](Br)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.CO>[OH-].[Na+].O>[OH:12][CH2:11][C:3]1[O:19][C:5]([CH3:9])=[CH:6][C:7](=[O:8])[C:2]=1[O:1][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 7498Benzyl BromideHCID 695214H-Pyran-4-one, 5-hydroxy-2-methyl-HCID 546900063-Hydroxy-N,1,6-trimethyl-4-oxo-1,4-dihydropyridine-2-carboxamide

Product 1

HCID 111394092-hydroxymethyl-3-benzyloxy-6-methyl-pyran-4(1H)-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 14798Sodium HydroxideSolvent

Procedure

3-Hydroxy-N,1,6-trimethyl-4-oxo-1,4-dihydropyridine-2-carboxamide has been prepared by the method, described in examples 45 to 48, 53, and 58 of WO98/154318. Allomaltol (1) is converted to 2-(1-hydroxymethyl)-6-methylpyromeconic acid (2) according to the procedure described in FR1516463. The 2-(1-hydroxymethyl)-6-methylpyromeconic acid (2) is reacted with benzyl bromide in sodium hydroxide in a 10:1 mixture of methanol and water to give the 2-hydroxymethyl-3-benzyloxy-6-methyl-pyran-4(1H)-one (3) which is then oxidized with diemthyl sulfoxide and sulfur trioxide.pyridine complex to give 2-formyl-3-benzyloxy-6-methyl-pyran-4(1H)-one (4). Oxidation of the 2-formyl derivative with sulfamic acid and sodium hypochlorite in acetone and water affords 2-carboxyl-3-benzyloxy-6-methyl-pyran-4(1H)-one (5). The 2-carboxyl derivative is reacted with dicyclohexyldiimide and 2-mercaptothiazoline and 4-dimethylaminopyridine to give the 3-(2-carbonyl-3-benzyloxy-6-methyl-4(1H)-pyran-2-yl)-1,3-thiazolidine-2-thione (6) which is reacted with methylamine in tetrahydrofuran to give 3-benzyloxy-6-methyl-4(1H)-pyran-2-yl)-2-carboxy-(N-methyl)-amide (7). The 3-benzyloxy-6-methyl-4(1H)-pyran-2-yl)-2-carboxy-(N-methyl)-amide (7) is converted to 1,6-dimethyl-3-benzyloxy-4(1H)-pyridinone-2-carboxy-)N-methyl)-amide (8) with methylamine in alcohol. The 3-benzyloxy derivative was deprotected with hydrogenation using Pd/C in dimethylformamide as illustrated in Scheme 1 to give 1,6-dimethyl-3-hydroxy-4(1H)-pyridinone-2-carboxy-)N-methyl)-amide (9):

Sources & evidence

ORD record
ord-5ae46ebd850840d4a034fe0154c8f5a8
Source dataset
uspto-grants-2002_11
Patent number
US06476229B1

Reaction notes

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