Methanol → HCID 22053625, compound

HRID 1830096Notes

Reaction equation

HRID 1830096 reaction equation
[OH2:1].O.[Sn](Cl)Cl.CC1C=C(C([N:15]2[C:21]3[CH:22]=[C:23]([C:26](N4CCCCC4)=[O:27])[CH:24]=[CH:25][C:20]=3[CH2:19][N:18]3[C:34](C(NCC4C=CN=CC=4)=O)=[CH:35][CH:36]=[C:17]3[CH2:16]2)=O)C=CC=1C1C=CC=CC=1C(F)(F)F.[CH3:57]O>Cl>[CH3:57][O:1][C:26]([C:23]1[CH:24]=[CH:25][C:20]2[CH2:19][N:18]3[CH:34]=[CH:35][CH:36]=[C:17]3[CH2:16][NH:15][C:21]=2[CH:22]=1)=[O:27]

Participants

5

Reactant 3

HCID 887MethanolHCID 61436Stannous chloride dihydrateHCID 10233688HCID 10233688, compound

Product 1

HCID 22053625HCID 22053625, compound

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Conditions

Temperature
40 °C

Procedure

To a stirred solution of tin(II) chloride dihydrate (23 g, 3.5 eq) in 2 N hydrochloric acid (106 mL) was added the [4-(2-formyl-1H-pyrrole-1-yl)methyl]-3-nitro]-benzoic acid methyl ester of Step A (8 g). Methanol (200 mL) was then added to this solution and the reaction mixture was stirred at 40° C. for 2 hours. The reaction was then cooled to room temperature, quenched by the addition of saturated aqueous sodium carbonate (20 mL) and filtered through Celite. The filter pad was washed with methanol and hot ethyl acetate. The filtrate and washings were combined, concentrated in vacuo to a volume of 300 mL and extracted with ethyl acetate. The combined extracts were dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to a volume of 200 mL. Acetic acid (1 g) and 10% palladium on charcoal (1.5 g) were added and the mixture was hydrogenated overnight at atmospheric pressure. The reaction was then filtered through Celite and the solvent removed in vacuo to give a dark brown crystalline solid (16.4 g). This was dissolved in dichloromethane and filtered through a silica pad eluting with dichloromethane to provide the title compound as a yellow crystalline solid (11.7 g). Recrystallization from 1,2-dichloroethane yielded a yellow crystalline solid (5.7 g), m.p. 198–200° C.

Workup

  1. temperatureThe reaction was then cooled to room temperature
  2. customquenched by the addition of saturated aqueous sodium carbonate (20 mL)
  3. filtrationfiltered through Celite
  4. washThe filter pad was washed with methanol and hot ethyl acetate
  5. concentrationconcentrated in vacuo to a volume of 300 mL
  6. extractionextracted with ethyl acetate
  7. dry with materialThe combined extracts were dried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo to a volume of 200 mL
  10. additionAcetic acid (1 g) and 10% palladium on charcoal (1.5 g) were added
  11. waitthe mixture was hydrogenated overnight at atmospheric pressure
  12. filtrationThe reaction was then filtered through Celite
  13. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-4051c8cd624e4736abaee5ca61bbdd4e
Source dataset
uspto-grants-2006_06
Patent number
US07064120B2

Reaction notes

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