Tetramethyltin → 2-Butyl-6-fluoro-5-methoxy-4-methyl-1-indanone

HRID 7891Notes

Reaction equation

HRID 7891 reaction equation
Br[C:2]1[C:10]([O:11][CH3:12])=[C:9]([F:13])[CH:8]=[C:7]2[C:3]=1[CH2:4][CH:5]([CH2:15][CH2:16][CH2:17][CH3:18])[C:6]2=[O:14].[CH3:19][Sn](C)(C)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl-].[Li+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CN(C)C=O>[CH2:15]([CH:5]1[CH2:4][C:3]2[C:7](=[CH:8][C:9]([F:13])=[C:10]([O:11][CH3:12])[C:2]=2[CH3:19])[C:6]1=[O:14])[CH2:16][CH2:17][CH3:18]

Participants

7

Reactant 4

HCID 11661TetramethyltinHCID 11776TriphenylphosphineHCID 433294Lithium ChlorideHCID 219909064-Bromo-2-butyl-6-fluoro-5-methoxy-1-indanone

Product 1

HCID 219908632-Butyl-6-fluoro-5-methoxy-4-methyl-1-indanoneYield 24.5%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-bromo-2-butyl-6-fluoro-5-methoxy-1-indanone (1.86 g, 5.94 mmol), bis(triphenylphosphine)palladium(II) chloride (208 mg, 0.297 mmol), tetramethyltin (0.989 mL, 7.128 mmol), triphenylphosphine (156 mg, 0.594 mmol), lithium chloride (504 mg, 11.88 mmol), and anhydrous N,N-dimethyl-formamide (11.9 mL) was placed under a nitrogen atmosphere, stirred, and heated in an oil bath at 100° C. for 22 hours. After cooling to room temperature, the mixture was evaporated under vacuum. The residue in EtOAc (150 mL) was washed with water (4×100 mL) and brine (50 mL), dried over MgSO4, filtered, and evaporated under vacuum to an oil (2.15 g). The crude product was purified by chromatography on EM silica gel 60 (2.5×29 cm column), eluting with CH2Cl2 (50 mL fore-run followed by 8 mL fractions). Fractions 20-28 were combined and evaporated under vacuum to provide 2-butyl-6-fluoro-5-methoxy-4-methyl-1-indanone (365 mg) as an oil.

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe mixture was evaporated under vacuum
  3. washThe residue in EtOAc (150 mL) was washed with water (4×100 mL) and brine (50 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated under vacuum to an oil (2.15 g)
  7. customThe crude product was purified by chromatography on EM silica gel 60 (2.5×29 cm column)
  8. washeluting with CH2Cl2 (50 mL fore-run followed by 8 mL fractions)
  9. customevaporated under vacuum

Sources & evidence

ORD record
ord-270913168eb241f99a23be25455ccdcc
Source dataset
uspto-grants-2006_08
Patent number
US07087599B2

Reaction notes

Loading…