HCID 14154011, compound → HCID 14533810, compound

HRID 1723502Notes

Reaction equation

HRID 1723502 reaction equation
[CH3:1][O:2][C:3](=[O:15])[CH2:4][C:5]1([CH2:13][CH3:14])[CH2:10][CH2:9][CH:8]=[C:7]([Br:11])[C:6]1=[O:12].[CH2:16]([Mg]Cl)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>O1CCCC1.[Br-].[Zn+2].[Br-]>[CH3:1][O:2][C:3](=[O:15])[CH2:4][C:5]1([CH2:13][CH3:14])[CH2:10][CH2:9][CH:8]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:7]([Br:11])[C:6]1=[O:12]

Participants

5

Reactant 2

HCID 14154011HCID 14154011, compoundHCID 178418336HCID 178418336, compound3×

Product 1

HCID 14533810HCID 14533810, compound

Reagents, catalysts & solvents 2

HCID 10421208Zinc bromideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 3-bromo-1-ethyl-2-oxocyclohex-3-eneacetic acid methyl ester (10 g, 36.3 mmol, as prepared in Example 1) and copper (I) bromide-dimethyl sulfide complex (3.63 mmol, 746 mg) in 107 mL of dry tetrahydrofuran was stirred at 0° C. under nitrogen and treated with anhydrous zinc bromide (36.3 mmol, 8.17 g). After 5 minutes, the mixture was treated dropwise with 36.3 mmol of benzylmagnesium chloride (18.2 mL of 2M in THF). After 45 minutes, another 8 mmol of benzylmagnesium chloride were added followed by 350 mg of copper (I) bromide-dimethyl sulfide complex and then another 16 mmol of benzylmagnesium chloride. The reaction was quenched with 150 mL of 1M HCl and extracted with 4×50 mL of ether. The extracts were conbined, dried over magnesium sulfate, and concentrated affording 3-bromo-1-ethyl-2-oxo-4-(phenylmethyl)cyclohexaneacetic acid methyl ester. This was then stirred in a solution of 74 mL of N,N-dimethylformamide and 35 mL of water and treated with 109 mmol (18.96 g) of sodium dithionite. The mixture was heated at 55° C. under nitrogen for 20 minutes, poured into 200 mL of water and extracted with 4×100 mL of 1:1 ether-petroleum ether. The extracts were combined, washed with 100 mL of water and 100 mL of saturated sodium bicarbonate (aq), dried over magnesium sulfate, and concentrated affording 10.48 g (36.3 mmol, 100% crude yield) of product as a pale yellow oil. Analysis by capillary GC demonstrated a 4.41:1 ratio of diastereomers, with the cis isomer predominating. The reduction of the intermediate 3-bromo-1-ethyl- 2-oxo-4-(phenylmethyl)cyclohexaneacetic acid methyl ester to the title compound can also be carried out as described in Example 3.

Workup

  1. waitAfter 45 minutes
  2. customThe reaction was quenched with 150 mL of 1M HCl
  3. extractionextracted with 4×50 mL of ether
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-01ce7284d1174869b4509641e94467a9
Source dataset
uspto-grants-1989_08
Patent number
US04861910

Reaction notes

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