Ammonium fluoride → HCID 68890591, compound

HRID 853098Notes

Reaction equation

HRID 853098 reaction equation
[C:1]([O:5][C:6](=[O:33])[NH:7][CH2:8][C@H:9]([N:11]1[C:19]2[C:14](=[CH:15][C:16]([Br:21])=[C:17]([CH3:20])[CH:18]=2)[CH:13]=[C:12]1[CH:22](C(C)(C)C(C)C)O[SiH](C)C)[CH3:10])([CH3:4])([CH3:3])[CH3:2].[F-].[NH4+]>CO>[C:1]([O:5][C:6]([N:7]1[CH2:8][C@@H:9]([CH3:10])[N:11]2[C:19]3[CH:18]=[C:17]([CH3:20])[C:16]([Br:21])=[CH:15][C:14]=3[CH:13]=[C:12]2[CH2:22]1)=[O:33])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 25516Ammonium fluorideHCID 131724706HCID 131724706, compound

Product 1

HCID 68890591HCID 68890591, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 0.75 g (R)-(2-{5-bromo-2-[dimethyl-(1,1,2-trimethyl-propyl)-silanyloxymethyl]-6-methyl-indol-1-yl}-propyl)-carbamic acid tert-butyl ester and 0.52 g ammonium fluoride in 7.5 ml methanol was stirred 18 h at room temperature. The reaction mixture was partitioned between water and ethyl acetate. The phases were separated and the organic phase was washed with 10% citric acid, 10% sodium bicarbonate and brine, dried over magnesium sulfate and evaporated to dryness. The residue was taken up in 6 ml dichloromethane and 0.59 g manganese dioxide was added. The mixture was stirred 2 h at room temperature. The solids were removed by filtration over dicalite and the filtrate was evaporated to dryness. The residue was taken up in 5 ml dichloromethane and 0.072 ml acetic acid and 1.00 g molecular sieve (powder, 4 Å) were added. To the resulting suspension was added 0.536 g triacetoxyborohydride, and the mixture was stirred 1 h at room temperature. Another 0.536 g triacetoxyborohydride was added and the mixture was stirred 1 h. The solids were removed by filtration over dicalite and the filtrate was purified by chromatography on silica gel with hexane:ethyl acetate=2:1 to yield 0.295 g of the title compound as a yellow solid melting at 113–114° C. after crystallisation from hexane.

Workup

  1. customThe reaction mixture was partitioned between water and ethyl acetate
  2. customThe phases were separated
  3. washthe organic phase was washed with 10% citric acid, 10% sodium bicarbonate and brine
  4. dry with materialdried over magnesium sulfate
  5. customevaporated to dryness
  6. addition0.59 g manganese dioxide was added
  7. stirringThe mixture was stirred 2 h at room temperature
  8. customThe solids were removed by filtration over dicalite
  9. customthe filtrate was evaporated to dryness
  10. addition0.072 ml acetic acid and 1.00 g molecular sieve (powder, 4 Å) were added
  11. additionTo the resulting suspension was added 0.536 g triacetoxyborohydride
  12. stirringthe mixture was stirred 1 h at room temperature
  13. additionAnother 0.536 g triacetoxyborohydride was added
  14. stirringthe mixture was stirred 1 h
  15. customThe solids were removed by filtration over dicalite
  16. customthe filtrate was purified by chromatography on silica gel with hexane

Sources & evidence

ORD record
ord-b4dd5880093b47fbb82c3ec1bafd0df0
Source dataset
uspto-grants-2007_08
Patent number
US07253281B2

Reaction notes

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