2,2-Dimethyl-1,3-dioxane-4,6-dione → Ethyl orthoformate

HRID 2241178Notes

Reaction equation

HRID 2241178 reaction equation
[CH2:1]([O:3][CH:4]([O:8][CH2:9][CH3:10])[O:5][CH2:6][CH3:7])[CH3:2].[CH3:11][C:12]1([CH3:20])[O:17][C:16](=[O:18])[CH2:15][C:14](=[O:19])[O:13]1.[CH3:21][O:22][C:23]1[CH:35]=[CH:34][C:26]([CH2:27][N:28]2[C:32]([NH2:33])=[CH:31][CH:30]=[N:29]2)=[CH:25][CH:24]=1>>[CH3:21][O:22][C:23]1[CH:24]=[CH:25][C:26]([CH2:27][N:28]2[C:32]([NH:33][CH:1]=[C:15]3[C:16](=[O:18])[O:17][C:12]([CH3:20])([CH3:11])[O:13][C:14]3=[O:19])=[CH:31][CH:30]=[N:29]2)=[CH:34][CH:35]=1.[CH2:1]([O:3][CH:4]([O:8][CH2:9][CH3:10])[O:5][CH2:6][CH3:7])[CH3:2]

Participants

5

Reactant 3

HCID 162492,2-Dimethyl-1,3-dioxane-4,6-dioneHCID 31214Ethyl orthoformateHCID 31612621-((4-methoxyphenyl)methyl)-1H-pyrazol-5-amine

Product 2

HCID 31214Ethyl orthoformateHCID 672206271,3-Dioxane-4,6-dione, 5-[[[1-[(4-methoxyphenyl)methyl]-1H-pyrazol-5-yl]amino]methylene]-2,2-dimethyl-

Conditions

Temperature
80 °C

Procedure

A stirred mixture of triethoxymethane (339 mL, 2037 mmol), and 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum's acid) (35.2 g, 244 mmol) was heated to 80° C. for 1 hour. A suspension of 1-(4-methoxybenzyl)-1H-pyrazol-5-amine [41.4 g, 204 mmol; prepared according to the procedure described by Misra, R. N., et al. Bioorg. Med. Chem. Lett. 2003, 13, 1133-1136, except desalting was performed as follows: 1-(4-methoxybenzyl)-1H-pyrazol-5-amine hydrochloride (44 g) was partitioned between MTBE (300 mL) and 1N aqueous NaOH (300 mL), after separating the phases, the aqueous suspension was re-extracted with MTBE (8×100 mL), followed by drying (Na2SO4) the combined organic phases, and concentration in vacuo to obtain the free-based 1-(4-methoxybenzyl)-1H-pyrazol-5-amine (30 g)] in triethoxymethane (339 mL, 2037 mmol) was added at once and heating at 80° C. was continued for 18 hours under N2. After cooling to room temperature, toluene azeotrope (2×200 mL) was utilized to remove EtOH. The resulting suspension was diluted with diethyl ether (500 mL) and filtered to obtain a yellow solid (33.5 g, 46%). 1H NMR (400 MHz, CDCl3) δ 11.13 (d, J=13 Hz, 1H), 8.26 (d, J=13 Hz, 1H), 7.50 (d, J=2 Hz, 1H), 7.25 (d, J=9 Hz, 2H), 6.88 (d, J=9 Hz, 2H), 6.21 (d, J=2 Hz, 1H), 5.28 (s, 2H), 3.78 (s, 3H), 1.74 (s, 6H).

Workup

  1. customprepared
  2. custom1-(4-methoxybenzyl)-1H-pyrazol-5-amine hydrochloride (44 g) was partitioned between MTBE (300 mL) and 1N aqueous NaOH (300 mL)
  3. customafter separating the phases
  4. extractionthe aqueous suspension was re-extracted with MTBE (8×100 mL)
  5. dry with materialby drying (Na2SO4)
  6. concentrationthe combined organic phases, and concentration in vacuo

Sources & evidence

ORD record
ord-6c2d0a0b09764182a79e702512106761
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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