Formaldehyde → 2-Butyl-4-chloro-6-fluoro-5-methoxy-1-indanone

HRID 7895

Reaction equation

HRID 7895 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:11](=[O:17])[CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH:5]=[C:6]([F:10])[C:7]=1[O:8][CH3:9].C=O.[C:20](=O)([O-])[O-].[K+].[K+]>CO>[CH2:13]([CH:12]1[CH2:20][C:3]2[C:4](=[CH:5][C:6]([F:10])=[C:7]([O:8][CH3:9])[C:2]=2[Cl:1])[C:11]1=[O:17])[CH2:14][CH2:15][CH3:16]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 11430Potassium CarbonateHCID 219909381-(3-Chloro-5-fluoro-4-methoxyphenyl)-1-hexanone

Product 1

HCID 219908612-Butyl-4-chloro-6-fluoro-5-methoxy-1-indanone

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of the crude 1-(3-chloro-5-fluoro-4-methoxyphenyl)-1-hexanone from step 1, methanol (8.7 mL), 37% aqueous formaldehyde (0.786 mL, 10.5 mmol), and potassium carbonate (1.2 g, 8.72 mmol) was stirred and heated in an oil bath at 50° C. for 7 hours. The mixture was evaporated under vacuum and the residue partitioned between EtOAc (100 mL) and water (100 mL) containing 2N HCl (10 mL). The organic phase was washed with brine (50 mL), dried over MgSO4, filtered, and evaporated under vacuum to an oil (1.86 g) consisting of predominantly 1-(3-chloro-5-fluoro-4-methoxyphenyl)-2-(methoxymethyl)-1-hexanone.

Workup

  1. customThe mixture was evaporated under vacuum
  2. customthe residue partitioned between EtOAc (100 mL) and water (100 mL)
  3. additioncontaining 2N HCl (10 mL)
  4. washThe organic phase was washed with brine (50 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated under vacuum to an oil (1.86 g)

Sources & evidence

ORD record
ord-644c4332f59e457193dc2c4b5fdfdc26
Source dataset
uspto-grants-2006_08
Patent number
US07087599B2

Linked notes

Loading…