Water → 3-(1,1,1-Trifluoropropan-2-yloxy)phenoxathiine 10,10-dioxide

HRID 1872874Notes

Reaction equation

HRID 1872874 reaction equation
[F:1][C:2]([F:7])([F:6])[CH:3]([OH:5])[CH3:4].[H-].[Na+].F[C:11]1[CH:12]=[CH:13][C:14]2[S:15](=[O:26])(=[O:25])[C:16]3[C:21]([O:22][C:23]=2[CH:24]=1)=[CH:20][CH:19]=[CH:18][CH:17]=3.O>CN(C)C(=O)C>[F:1][C:2]([F:7])([F:6])[CH:3]([CH3:4])[O:5][C:11]1[CH:12]=[CH:13][C:14]2[S:15](=[O:25])(=[O:26])[C:16]3[C:21]([O:22][C:23]=2[CH:24]=1)=[CH:20][CH:19]=[CH:18][CH:17]=3

Participants

6

Reactant 4

HCID 962WaterHCID 97741,1,1-Trifluoro-2-propanolHCID 24758Sodium hydrideHCID 186877423-Fluorophenoxathiin 10,10-dioxide

Product 1

HCID 99280813-(1,1,1-Trifluoropropan-2-yloxy)phenoxathiine 10,10-dioxideYield 79.7%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent3×

Conditions

Temperature
12.5 °C

Procedure

(rac)-1,1,1-Trifluoro-2-propanol (Oakwood) (189.30 g, 1.66 mole) in N,N-dimethylacetamide (200 mL) was added to a stirred, ice-bath cooled mixture of hexanes washed sodium hydride (60% dispersion in mineral oil) (Aldrich) (66.40 g, 1.66 mole) and N,N-dimethylacetamide (1900 mL) under nitrogen. The reaction was stirred at ambient temperature (5-20° C.) for 0.5 hour. 3-Fluorophenoxathiin 10,10-dioxide (Example 47) (277.78 g, 1.11 mole) in N,N-dimethylacetamide (1800 mL) was added at a bath temperature of 5-15° C. and stirred at ambient temperature for 1 hour. The reaction mixture was poured into water (8 L) and extracted with ethyl acetate (3 L, 2 L). The combined extracts were washed with water (4 L, 2 L), brine (0.5 L), dried over magnesium sulfate and filter. The volatiles were removed by spin evaporation in vacuo. The residue was stirred with hexanes (1 L) and collected by suction filtration to give 399.51 g of crude product. Recrystallization from 2-propanol (1.5 L) gave 304.62 g (79% yield) of (rac)-3-(2,2,2-trifluoro-1-methylethoxy)phenoxathiin 10,10-dioxide, m.p. 98-100 C.

Workup

  1. temperaturecooled
  2. stirringstirred at ambient temperature for 1 hour
  3. extractionextracted with ethyl acetate (3 L, 2 L)
  4. washThe combined extracts were washed with water (4 L, 2 L), brine (0.5 L)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfilter
  7. customThe volatiles were removed by spin evaporation in vacuo
  8. stirringThe residue was stirred with hexanes (1 L)
  9. filtrationcollected by suction filtration
  10. customto give 399.51 g of crude product
  11. customRecrystallization from 2-propanol (1.5 L)

Sources & evidence

ORD record
ord-d4d294a6c7ba43d588f5fe6f32bdab0a
Source dataset
uspto-grants-2000_08
Patent number
US06110961

Reaction notes

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