Acetic Acid → 5-((3,3-Difluorocyclobutyl)methyl)-2,2-dimethyl-1,3-dioxane-4,6-dione

HRID 58850Notes

Reaction equation

HRID 58850 reaction equation
[F:1][C:2]1([F:18])[CH2:5][CH:4]([C:6]([CH:8]2[C:13](=[O:14])[O:12][C:11]([CH3:16])([CH3:15])[O:10][C:9]2=[O:17])=O)[CH2:3]1.C(O)(=O)C.[BH4-].[Na+]>C1COCC1>[F:18][C:2]1([F:1])[CH2:5][CH:4]([CH2:6][CH:8]2[C:9](=[O:17])[O:10][C:11]([CH3:16])([CH3:15])[O:12][C:13]2=[O:14])[CH2:3]1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 4311764Sodium borohydrideHCID 668781495-[(3,3-Difluorocyclobutyl)carbonyl]-2,2-dimethyl-1,3-dioxane-4,6-dione

Product 1

HCID 1176905515-((3,3-Difluorocyclobutyl)methyl)-2,2-dimethyl-1,3-dioxane-4,6-dioneYield 58%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 5-(3,3-difluorocyclobutanecarbonyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (15.0 g, 57.3 mmol) in THF (200 mL) was cooled to −5° C. and acetic acid (38 g, 0.63 mol) was added. The mixture was stirred for 5 min and sodium borohydride (6.5 g, 0.17 mol) was added in portions. The reaction mixture was stirred for 2 h at −5° C. and then poured into ice water (200 mL). The resulting mixture was extracted with EtOAc (300 mL×3). The organic extracts were combined, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by flash column chromatography on silica gel (dichloromethane/methanol=100:1 to 30:1) to afford 5-((3,3-difluorocyclobutyl)methyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (8.2 g, 58% yield).

Workup

  1. stirringThe reaction mixture was stirred for 2 h at −5° C.
  2. extractionThe resulting mixture was extracted with EtOAc (300 mL×3)
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by flash column chromatography on silica gel (dichloromethane/methanol=100:1 to 30:1)

Sources & evidence

ORD record
ord-b8cad9fc48e84000a0a91b5ad3986e6e
Source dataset
uspto-grants-2016_09
Patent number
US09434761B2

Reaction notes

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