Sodium borohydride → HCID 86700855, compound

HRID 881751Notes

Reaction equation

HRID 881751 reaction equation
[CH3:1][O:2][C:3](=[O:21])[CH2:4][C:5]12[CH2:13][CH2:12][C:8]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)([CH:9](Br)[CH2:10]1)[O:7][CH2:6]2.[BH4-].[Na+]>CO.C(OCC)(=O)C.O1CCCC1.ClC1C=CC=CC=1.[Ni](Cl)Cl>[CH3:1][O:2][C:3](=[O:21])[CH2:4][C:5]12[CH2:13][CH2:12][C:8]([C:14]3[CH:15]=[CH:16][C:17]([Cl:20])=[CH:18][CH:19]=3)([CH2:9][CH2:10]1)[O:7][CH2:6]2

Participants

8

Reactant 2

HCID 4311764Sodium borohydrideHCID 86700854HCID 86700854, compound

Product 1

HCID 86700855HCID 86700855, compoundYield 66%

Reagents, catalysts & solvents 5

HCID 24385Nickel DichlorideCatalystHCID 887MethanolSolventHCID 7964ChlorobenzeneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of [6-bromo-1-(4-chloro-phenyl)-2-oxa-bicyclo[2.2.2]oct-4-yl]-acetic acid methyl ester (0.75 g, 2.007 mmol) and nickel (II) chloride (0.182 g, 1.405 mmol) in methanol (30 ml), ethyl acetate (15 ml), tetrahydrofuran (15 ml) and chlorobenzene (2 ml) at −30° C., was added carefully sodium borohydride (0.228 g, 6.02 mmol). The reaction mixture was allowed to warm to room temperature for 40 minutes. The solvent was removed under vacuum at room temperature and then water (20 ml) and EtOAc (100 ml) were added. The organic phase was separated and washed with brine, dried over Na2SO4 and concentrated. The residue was purified by flash chromatography (heptanes/acetone 2/1) to afford [1-(4-chloro-phenyl)-2-oxa-bicyclo[2.2.2]oct-4-yl]-acetic acid methyl ester (0.39 g, 66%) as white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.65-1.81 (m, 4H) 1.96 (t, J=8.00 Hz, 4H) 2.11 (s, 2H) 3.62 (s, 3H) 3.87 (s, 2H) 7.20 (d, J=8.60 Hz, 2H) 7.25 (d, J=8.60 Hz, 2H).

Workup

  1. customThe solvent was removed under vacuum at room temperature
  2. additionwater (20 ml) and EtOAc (100 ml) were added
  3. customThe organic phase was separated
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography (heptanes/acetone 2/1)

Sources & evidence

ORD record
ord-8b24622e1a3c4393b220a867ff3e8890
Source dataset
uspto-grants-2015_03
Patent number
US08993619B2

Reaction notes

Loading…