Sodium borohydride → HCID 58594757, compound

HRID 890837Notes

Reaction equation

HRID 890837 reaction equation
[BH4-].[Na+].[CH3:3][C:4]1([CH3:27])[O:8][C@H:7]([CH2:9][C@@H:10]2[C:16](=[O:17])[C:15]3[CH:18]=[C:19]([F:22])[CH:20]=[CH:21][C:14]=3[CH2:13][C:12]3[CH:23]=[CH:24][CH:25]=[CH:26][C:11]2=3)[CH2:6][O:5]1>C(O)(C)C.P([O-])([O-])([O-])=O>[CH3:3][C:4]1([CH3:27])[O:8][C@H:7]([CH2:9][C@@H:10]2[C@H:16]([OH:17])[C:15]3[CH:18]=[C:19]([F:22])[CH:20]=[CH:21][C:14]=3[CH2:13][C:12]3[CH:23]=[CH:24][CH:25]=[CH:26][C:11]2=3)[CH2:6][O:5]1

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 11530211HCID 11530211, compound2×

Product 1

HCID 58594757HCID 58594757, compoundYield 35%

Reagents, catalysts & solvents 2

HCID 1061PhosphateSolventHCID 3776IsopropanolSolvent

Procedure

Solid sodium borohydride (2.50 g, 66 mmol) was added in small portions within 15 min. into a magnetically stirred, ice-cooled solution of (11R) and (11S)-11-{[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-8-fluoro-5,11-dihydro-10H-dibenzo[a,d]cyclohepten-10-one (reaction mixture of intermediate 7 and 8 before separation) (65:35, 1278 mg, 3.75 mmol) in isopropanol (160 mL) and 0.5 M phosphate buffer (pH 7, 63 mL). Reaction mixture was stirred at 0° C. for additional 15 min., quenched with saturated aqueous NH4Cl (30 mL); organic phase was separated, aqueous solution extracted with ether (2×30 mL), combined organics washed with water (2×50 mL), then brine (50 mL), dried (MgSO4), evaporated in vacuo, to furnish crude mixture of two alcohols. HPLC separation (Waters 515 pump, 2 mL injection loop, Merck Hibar® 250×25 mm column LiChrosorb® SI 60 7 μm, Waters 2410 refractive index detector, EtOAc-hexane 30:70, 15 mL/min) gave pure intermediate 13 (10S,11S)-11-{[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-8-fluoro-10,11-dihydro-5H-diben-zo[a,d]cyclohepten-10-ol (449 mg, 1.31 mmol, 35%) as a colorless oil.

Workup

  1. customReaction mixture
  2. stirringwas stirred at 0° C. for additional 15 min.
  3. customquenched with saturated aqueous NH4Cl (30 mL)
  4. customorganic phase was separated
  5. extractionaqueous solution extracted with ether (2×30 mL)
  6. washcombined organics washed with water (2×50 mL)
  7. dry with materialbrine (50 mL), dried (MgSO4)
  8. customevaporated in vacuo
  9. customto furnish crude
  10. customHPLC separation (Waters 515 pump, 2 mL injection loop, Merck Hibar® 250×25 mm column LiChrosorb® SI 60 7 μm, Waters 2410 refractive index detector, EtOAc-hexane 30:70, 15 mL/min)

Sources & evidence

ORD record
ord-f1df63da35e44a20a8ddbcb1ec983981
Source dataset
uspto-grants-2006_02
Patent number
US06998494B2

Reaction notes

Loading…