Citric Acid → Methyl 1-(1-hydroxy-2-methylpropan-2-yl)-6-oxo-1,6-dihydropyridine-3-carboxylate

HRID 1878717Notes

Reaction equation

HRID 1878717 reaction equation
[NH2:1][C:2]([CH3:6])([CH3:5])[CH2:3][OH:4].[C:7]([O:11][CH3:12])(=[O:10])[C:8]#[CH:9].C[O-].[Na+].[C:16](O)(=O)[CH2:17][C:18](CC(O)=O)(C(O)=O)[OH:19]>CO.C(Cl)Cl>[OH:4][CH2:3][C:2]([N:1]1[C:18](=[O:19])[CH:17]=[CH:16][C:8]([C:7]([O:11][CH3:12])=[O:10])=[CH:9]1)([CH3:6])[CH3:5]

Participants

7

Reactant 4

HCID 311Citric AcidHCID 118072-Amino-2-methyl-1-propanolHCID 13536Methyl propiolateHCID 10942334Sodium Methoxide

Product 1

HCID 68820470Methyl 1-(1-hydroxy-2-methylpropan-2-yl)-6-oxo-1,6-dihydropyridine-3-carboxylate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

A solution of 2-amino-2-methyl-1-propanol (2 mL, 24 mmol) and methyl propiolate (5 mL, 61 mmol) in MeOH (10 mL) was appropriately sealed and heated to 120° C. for 30 min with microwaves. Sodium methoxide (25 wt. % in methanol, 4 mL, 73 mmol) was added and the solution was sealed and heated again to 120° C. for 30 min with microwaves. The mixture was partioned between CH2Cl2 (60 mL) and 10% citric acid (20 mL). The aqueous was repeatedly extracted with CH2Cl2 (4×15 mL). Combined organics dried over MgSO4 then concentrated onto dry silica (20 g). The residue was purified on 120 g silica eluting with 10-40% of 5% MeOH/CH2Cl2, and isolated as a yellow solid. MS (ESI pos. ion) m/z (MH+): 226. Calc'd exact mass for C11H15NO4: 225. 1H NMR (400 MHz, Chloroform-d) δ ppm 1.66 (s, 6 H) 3.86 (s, 3 H) 3.98 (s, 2 H) 6.49 (d, J=9.54 Hz, 1 H) 7.77-7.89 (m, 1 H) 8.42 (s, 1 H). 13C NMR (101 MHz, Chloroform-d) δ ppm 22.70, 50.08, 65.04, 66.57, 107.88, 119.17, 135.92, 138.43, 162.56, 162.98.

Workup

  1. customthe solution was sealed
  2. temperatureheated again to 120° C. for 30 min with microwaves
  3. extractionThe aqueous was repeatedly extracted with CH2Cl2 (4×15 mL)
  4. dry with materialCombined organics dried over MgSO4
  5. concentrationthen concentrated onto dry silica (20 g)
  6. customThe residue was purified on 120 g silica eluting with 10-40% of 5% MeOH/CH2Cl2
  7. customisolated as a yellow solid

Sources & evidence

ORD record
ord-14738ba7317f4492ba33d8760189a9a2
Source dataset
uspto-grants-2012_11
Patent number
US08314087B2

Reaction notes

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