Trimethyl borate → (1R)-1-(6-Bromo-2-pyridinyl)-1-pentanol

To a stirring solution of (S)-(−)-α,α-diphenyl-2-pyrrolidinemethanol (α,α-diphenyl-L-prolinol) (840 mg, 3.32 mmol) in THF (3 mL) was added drop-wise trimethylborate (0.45 mL, 3.97 mmol) at ambient temperature under nitrogen. After stirring for 1 h at this temperature, borane dimethylsulfide (2M in THF, 2.5 mL, 5.00 mmol) drop-wise over 3-4 minutes. After the effervescence had stopped, 1-(6-bromo-2-pyridinyl)-1-pentanone (797 mg, 3.29 mmol) in THF (3.6 mL) was added over 1 h using a syringe pump. The mixture was stirred for an additional 5 minutes and the reaction was then quenched with aqueous HCl (2N, 5 mL) and the reaction mixture stirred overnight at ambient temperature. The mixture was then reduced under vacuum and the residue partitioned between EtOAc (30 mL) and water (30 mL) and the layers separated. The aqueous was then re-extracted with EtOAc (30 mL) and the combined organic layer washed with brine (50 mL) and then reduced under vacuum to give an oil. Purification by SPE (silica, 20 g cartridge) eluting with cyclohexane:EtOAc (gradient 100:1 to 3:1) afforded the title compound as an oil (712 mg).

1. customthe reaction was then quenched with aqueous HCl (2N, 5 mL)
2. stirringthe reaction mixture stirred overnight at ambient temperature
3. customthe residue partitioned between EtOAc (30 mL) and water (30 mL)
4. customthe layers separated
5. extractionThe aqueous was then re-extracted with EtOAc (30 mL)
6. washthe combined organic layer washed with brine (50 mL)
7. customto give an oil
8. customPurification by SPE (silica, 20 g cartridge)
9. washeluting with cyclohexane

ORD-Eintrag

ord-e47ea27185d1413fac695b4271e5085a

Quelldatensatz

uspto-grants-2008_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07338960B2