2-Bromopyridine → 2-Chloro-7-(3-chloro-4-methoxy-phenyl)-5-cyclopentyl-5-hydroxy-3-oxo-heptanoic acid methyl ester

HRID 1453271Notes

Reaction equation

HRID 1453271 reaction equation
[CH3:1][O:2][C:3](=[O:9])[CH:4]([Cl:8])[C:5]([CH3:7])=[O:6].[H-].[Na+].[Li]CCCC.[Cl:17][C:18]1[CH:19]=[C:20]([CH2:26][CH2:27][C:28]([CH:30]2[CH2:34][CH2:33][CH2:32][CH2:31]2)=[O:29])[CH:21]=[CH:22][C:23]=1[O:24][CH3:25].BrC1C=CC(OC)=C(Cl)C=1.BrC1C=CC=CN=1>C1COCC1>[CH3:1][O:2][C:3](=[O:9])[CH:4]([Cl:8])[C:5](=[O:6])[CH2:7][C:28]([CH:30]1[CH2:34][CH2:33][CH2:32][CH2:31]1)([OH:29])[CH2:27][CH2:26][C:20]1[CH:21]=[CH:22][C:23]([O:24][CH3:25])=[C:18]([Cl:17])[CH:19]=1

Participants

8

Reactant 6

HCID 79732-BromopyridineHCID 24758Sodium hydrideHCID 107332Methyl 2-chloroacetoacetateHCID 30165374-Bromo-2-chloroanisoleHCID 219385963-(3-Chloro-4-methoxy-phenyl)-1-cyclopentyl-propan-1-oneHCID 178418339Butyllithium

Product 1

HCID 210622722-Chloro-7-(3-chloro-4-methoxy-phenyl)-5-cyclopentyl-5-hydroxy-3-oxo-heptanoic acid methyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

Methyl-2-chloroacetoacetate (2.5 g, 16.9 mmol) was added to a cooled 0° C. suspension of NaH (0.68 g, 16.9 mmol, 60% dispersion in mineral oil) in THF (30 ml). After 15 min the solution was cooled to −40° C. and n-BuLi (10.6 mL, 16.9 mmol, 1.6M in hexanes) was added. The resulting dianion was stirred for an additional 30 min and then treated with a solution of 3-(3-Chloro-4-methoxy-phenyl)-1-cyclopentyl-propan-1-one (1.5 g, 5.6 mmol, compound was prepared analogously to Step 1 of Example A(82), where 4-bromo-2-chloro-1-methoxybenzene was substituted in place of 2-Bromopyridine) in THF (10 ml). After stirring for 1 h at −40° C., the reaction mixture was quenched with saturated NH4Cl and extracted with EtOAc. The organic layers were washed with brine, dried with Na2SO4 and concentrated to an orange oil that was used without further purification.

Workup

  1. stirringAfter stirring for 1 h at −40° C.
  2. customthe reaction mixture was quenched with saturated NH4Cl
  3. extractionextracted with EtOAc
  4. washThe organic layers were washed with brine
  5. dry with materialdried with Na2SO4
  6. concentrationconcentrated to an orange oil that
  7. customwas used without further purification

Sources & evidence

ORD record
ord-a1e57f47b0ef47658f3ffd586f847a8a
Source dataset
uspto-grants-2009_01
Patent number
US07473790B2

Reaction notes

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