Phosphoric Acid → HCID 10133523, compound

HRID 2298430Notes

Reaction equation

HRID 2298430 reaction equation
C([O:4][C:5](=O)[CH:6]([CH2:13][C:14]1[C:15]([O:27][C:28]2[C:33]([CH3:34])=[CH:32][C:31]([CH3:35])=[CH:30][C:29]=2[CH3:36])=[N:16][C:17]([CH3:26])=[CH:18][C:19]=1[NH:20][CH:21]([CH2:24][CH3:25])[CH2:22][CH3:23])C(OC(C)C)=O)(C)C.P(=O)(O)(O)O>>[CH2:22]([CH:21]([N:20]1[C:19]2[C:14](=[C:15]([O:27][C:28]3[C:33]([CH3:34])=[CH:32][C:31]([CH3:35])=[CH:30][C:29]=3[CH3:36])[N:16]=[C:17]([CH3:26])[CH:18]=2)[CH2:13][CH2:6][C:5]1=[O:4])[CH2:24][CH3:25])[CH3:23]

Participants

3

Reactant 2

HCID 1004Phosphoric AcidHCID 53724574HCID 53724574, compound

Product 1

HCID 10133523HCID 10133523, compoundYield 98%

Conditions

Temperature
73 °C

Procedure

A mixture of 2-[4-(1-ethyl-propylamino)-6-methyl-2-(2,4,6-trimethyl-phenoxy)-pyridin-3-ylmethyl]-malonic acid diisopropyl ester (40 mg, 0.078 mmol) and 85% phosphoric acid was heated at 73° C. overnight, and then heated at 133° C. for 1 hour. The reaction mixture was cooled, quenched with water and extracted with ethyl acetate. The organic layer was washed with brine, dried and concentrated to give a brown oil. The oil residue was purified through silica gel column chromatography using 3% ethyl acetate in hexane as eluent to give 28 mg (98%) of the title compound. 1H NMR (CDCl3) δ 6.89(s,2H), 6.56(s,1H), 4.4(m,1H), 3.00(m,2H), 2.67(m,2H), 2.31(s,3H), 2.25(s,3H), 2.07(s,6H), 1.86(m,4H), 0.90(t,6H) ppm.

Workup

  1. temperatureheated at 133° C. for 1 hour
  2. temperatureThe reaction mixture was cooled
  3. customquenched with water
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with brine
  6. customdried
  7. concentrationconcentrated
  8. customto give a brown oil
  9. customThe oil residue was purified through silica gel column chromatography

Sources & evidence

ORD record
ord-7697922d71094e959c06ec780789dc62
Source dataset
uspto-grants-2002_12
Patent number
US06492520B1

Reaction notes

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