1-Bromo 4-fluoronaphthalene → HCID 58468275, compound

HRID 2094645Notes

Reaction equation

HRID 2094645 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([F:12])=[CH:4][CH:3]=1.[Li]CCCC.[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([C:26](=[O:44])[C@@H:27]([C:31]2[CH:43]=[CH:42][C:34]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])=[CH:33][CH:32]=2)[CH2:28][CH2:29][CH3:30])=[CH:22][CH:21]=1>C1COCC1>[F:12][C:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:2]([C:26]([OH:44])([C:23]2[CH:22]=[CH:21][C:20]([O:19][CH3:18])=[CH:25][CH:24]=2)[C@@H:27]([C:31]2[CH:43]=[CH:42][C:34]([C:35]([O:37][C:38]([CH3:39])([CH3:41])[CH3:40])=[O:36])=[CH:33][CH:32]=2)[CH2:28][CH2:29][CH3:30])=[CH:3][CH:4]=1

Participants

5

Reactant 3

HCID 676471-Bromo 4-fluoronaphthaleneHCID 67436804HCID 67436804, compoundHCID 178418339Butyllithium

Product 1

HCID 58468275HCID 58468275, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1-bromo-4-fluoronaphthalene (229 mg, 1.02 mmol) in THF (6 mL) at −78° C. was added BuLi (2.5 M in hexanes, 0.434 mL, 1.086 mmol), then the solution was stirred for one hour. A solution of t-butyl (R)-4-[2-(4-methoxyphenyl)-1-propylethan-2-one-1-yl]benzoate (prepared using the procedure for INTERMEDIATE 4, 250 mg, 0.678 mmol) in THF (2 mL) was added and the solution was stirred for an additional hour. The solution was quenched with saturated NH4Cl (aq), then diluted with EtOAc (50 mL). The organic layer was separated, washed with water then brine, dried over MgSO4, filtered, then concentrated. The residue was purified by silica gel chromatography eluting with 0-20% EtOAc/hexanes to afford the title compound. LC1 1.30 min. [M+H−H2O]+ 497.

Workup

  1. additionwas added
  2. stirringthe solution was stirred for an additional hour
  3. customThe solution was quenched with saturated NH4Cl (aq)
  4. additiondiluted with EtOAc (50 mL)
  5. customThe organic layer was separated
  6. washwashed with water
  7. dry with materialbrine, dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by silica gel chromatography
  11. washeluting with 0-20% EtOAc/hexanes

Sources & evidence

ORD record
ord-c297ae51058c423dbcf38e21a5c3d4b0
Source dataset
uspto-grants-2013_05
Patent number
US08445538B2

Reaction notes

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