Lithium Hydroxide → HCID 86663670, compound

HRID 879075Notes

Reaction equation

HRID 879075 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH:14]3[CH2:16][CH2:15]3)=[C:10]([CH:17]=[C:18]3[C:22]([CH3:24])([CH3:23])[O:21][C:20]([CH3:26])([CH3:25])[C:19]3=[O:27])[CH:9]=2)=[C:4]([F:28])[CH:3]=1.[OH-:29].[Li+]>CO.OO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH:14]3[CH2:16][CH2:15]3)=[C:10]([CH:17]3[C:18]4([C:19](=[O:27])[C:20]([CH3:26])([CH3:25])[O:21][C:22]4([CH3:23])[CH3:24])[O:29]3)[CH:9]=2)=[C:4]([F:28])[CH:3]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 66823358HCID 66823358, compound

Product 1

HCID 86663670HCID 86663670, compoundYield 438.7%

Reagents, catalysts & solvents 2

HCID 784Hydrogen PeroxideCatalystHCID 887MethanolSolvent

Procedure

To a solution of 4-[1-(4′-chloro-4-cyclopropyl-2′-fluorobiphenyl-3-yl)methylidene]-2,2,5,5-tetramethyldihydrofuran-3-one (19.80 g, 0.050 mol) in methanol (830 ml) at 35° C. is added 50% aqueous hydrogen peroxide (5.00 ml, 0.075 mmol), followed immediately by 2M lithium hydroxide (5.00 ml, 0.01 mol) solution. The mixture is stirred at this temperature for a further 2 hours, then allowed to cool to room temperature. Then reaction mixture is quenched with 10% sodium metabisulfite (negative KI-starch indicator test) then diluted with diethyl ether. Most of the methanol is removed under vacuum, and the crude mixture is partitioned between distilled water and diethyl ether. The aqueous phase is further extracted with diethyl ether (×2), then all organics are combined and washed with saturated sodium bicarbonate (×2) then brine. After anhydrousing over magnesium sulfate the suspension is filtered and the filtrate concentrated in vacuo to afford 2-(4′-chloro-4-cyclopropyl-2′-fluorobiphenyl-3-yl)-4,4,6,6-tetramethyl-1,5-dioxa-spiro[2.4]heptan-7-one (18.2 g) as an orange foam. This material is of sufficient purity to use directly in the next step without further purification.

Workup

  1. customThen reaction mixture
  2. customis quenched with 10% sodium metabisulfite (negative KI-starch indicator test)
  3. additionthen diluted with diethyl ether
  4. customMost of the methanol is removed under vacuum
  5. customthe crude mixture is partitioned
  6. distillationbetween distilled water and diethyl ether
  7. extractionThe aqueous phase is further extracted with diethyl ether (×2)
  8. washwashed with saturated sodium bicarbonate (×2)
  9. filtrationis filtered
  10. concentrationthe filtrate concentrated in vacuo

Sources & evidence

ORD record
ord-7cd9b44a91bb40a6b60b6e446e5fcb96
Source dataset
uspto-grants-2015_03
Patent number
US08987476B2

Reaction notes

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