Methanol → HCID 22327231, compound

HRID 495523Notes

Reaction equation

HRID 495523 reaction equation
[H-].C([Al+]CC(C)C)C(C)C.[F:11][C:12]1[CH:42]=[CH:41][CH:40]=[C:39]([F:43])[C:13]=1[CH2:14][N:15]1[C:20]([CH3:21])=[C:19]([C:22](OCC)=[O:23])[C:18](=[O:27])[C:17]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([O:35][CH3:36])[C:30]=2[F:37])(Br)[CH:16]1[CH3:38].CC(C[AlH]CC(C)C)C.CO>C1COCC1.C(Cl)Cl>[F:11][C:12]1[CH:42]=[CH:41][CH:40]=[C:39]([F:43])[C:13]=1[CH2:14][N:15]1[C:20]([CH3:21])=[C:19]([CH:22]=[O:23])[C:18](=[O:27])[C:17]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([O:35][CH3:36])[C:30]=2[F:37])=[C:16]1[CH3:38]

Participants

6

Reactant 4

HCID 887MethanolHCID 14487Diisobutylaluminum hydrideHCID 21225700DiisobutylaluminumhydrideHCID 22327241HCID 22327241, compound

Product 1

HCID 22327231HCID 22327231, compound

Reagents, catalysts & solvents 1

HCID 21919333Tetrahydrofurane dichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

Diisobutylaluminum hydride (3.75 mmol, 3.75 ml of a 1.0M solution in hexanes ) was added dropwise to a stirring solution of 1-(2,6-difluorobenzyl)-2,6-dimethyl-3-(2-fluoro-3-methoxyphenyl)-3-bromo-5-ethoxycarbonyl-4-pyridone (1.12 g, 2.5 mmol) in THF/DCM (30 mL/ 12 mL), at −78° C. under N2. A suspension was formed at the end of the addition. After 1 hour, an additional aliquot of DIBAL-H (2.5 mmol, 2.5 mL of a 1.0 M solution in hexanes) was added. The reaction was stirred for 1 hour at −78° C. MeOH (50 mL) was carefully added to quench any unreacted DIBAL-H. The solution was concentrated, then partitioned between EtOAc and 1 M HCl. The organic layer was concentrated and purified using flash silica gel chromatography (100% hexanes to EtOAc/hexanes 3/2). The fourth spot which eluted was evaporated to give product as a cream colored solid. 1H NMR (CDCl3, 300 MHz) δ 10.55 (s, 1H), 6.80-7.75 (m, 6H), 5.36 (s, 2H), 3.90 (s, 3H), 2.79 (s, 3H), 2.27 (s, 3H); LCMS=402 (MH+).

Workup

  1. customA suspension was formed at the end of the addition
  2. customto quench any unreacted DIBAL-H
  3. concentrationThe solution was concentrated
  4. custompartitioned between EtOAc and 1 M HCl
  5. concentrationThe organic layer was concentrated
  6. custompurified
  7. washThe fourth spot which eluted
  8. customwas evaporated
  9. customto give product as a cream

Sources & evidence

ORD record
ord-1f4b16a53a414534bf15f027770e8aa3
Source dataset
uspto-grants-2005_09
Patent number
US06939883B2

Reaction notes

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