Methanol → HCID 59853561, compound

HRID 730530Notes

Reaction equation

HRID 730530 reaction equation
C(O[C:5]([C:7]1[N:8]([N:13]([C:19](=[O:26])[CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:14][CH2:15][CH:16]([CH3:18])[CH3:17])[CH:9]=[C:10]([F:12])[CH:11]=1)=[O:6])C=C.[O-]CC.[Na+].CO>C(O)C.ClCCl>[CH2:24]([O:23][C:21]([C:20]1[C:19](=[O:26])[N:13]([CH2:14][CH2:15][CH:16]([CH3:17])[CH3:18])[N:8]2[CH:9]=[C:10]([F:12])[CH:11]=[C:7]2[C:5]=1[OH:6])=[O:22])[CH3:25]

Participants

6

Reactant 3

HCID 887MethanolHCID 2723922Sodium ethoxideHCID 68777387HCID 68777387, compound

Product 1

HCID 59853561HCID 59853561, compoundYield 49.1%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 1-[(2-ethoxycarbonyl-acetyl)-(3-methyl-butyl)-amino]-4-fluoro-1H-pyrrole-2-carboxylic acid allyl ester (Example 14 h, 0.318 g, 0.898 mmol) in ethanol (10 mL) was added a 21% solution of sodium ethoxide in ethanol (0.728 g, 2.245 mmol) and the mixture was heated at 40° C. for 16 h. The solvent was removed in vacuo and the residue was purified by flash column chromatography (Merck silica gel 60, 40-63 μm, 20% ethyl acetate in hexanes, then 10% methanol in dichloromethane) to afford the desired product, 6-fluoro-4-hydroxy-1-(3-methyl-butyl)-2-oxo-1,2-dihydro-pyrrolo[1,2-b]pyridazine-3-carboxylic acid ethyl ester (0.137 g, 0.441 mmol, 49.1% yield) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ: 0.99 (3H, s), 1.00 (3H, s), 1.44 (3H, t, J=7.0 Hz), 1.58-1.63 (2H, m), 1.67-1.75 (1H, m), 4.18-4.22 (2H, m), 4.44 (2H, quartet, J=7.1 Hz), 6.55 (1H, m), 7.04 (1H, m).

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was purified by flash column chromatography (Merck silica gel 60, 40-63 μm, 20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-dbf8b2abef0d4f9ab2e7a070c2b2cd03
Source dataset
uspto-grants-2009_09
Patent number
US07582754B2

Reaction notes

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