Formaldehyde → HCID 59648502, compound

HRID 1363292Notes

Reaction equation

HRID 1363292 reaction equation
Br[C:2]([F:15])([F:14])[C:3]#[C:4][CH2:5][O:6][Si:7]([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8].[CH2:16]=[O:17].[In]>C1COCC1.O>[Si:7]([O:6][CH2:5][C:4]#[C:3][C:2]([F:15])([F:14])[CH2:16][OH:17])([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8].[F:15][C:2]([F:14])([CH2:16][OH:17])[C:3]#[C:4][CH2:5][OH:6].[CH2:5]([OH:6])[C:4]#[CH:3]

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 5359967IndiumHCID 11961725Silane, [(4-bromo-4,4-difluoro-2-butynyl)oxy](1,1-dimethylethyl)dimethyl-

Product 2

HCID 59648502HCID 59648502, compoundYield 44%HCID 86617321HCID 86617321, compoundYield 21%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

To a stirred solution of (4-bromo-4,4-difluoro-but-2-ynyloxy)-tert-butyl-dimethyl-silane (9.0 g, 30.1 mmol) and HCHO (37 wt % solution in water, 3.36 mL, 45.1 mmol) in THF/H2O (38.6 mL, 4/1, v/v) was added indium powder (4.14 g, 36.1 mmol) at rt. After stirring vigorously for 22 h, the reaction mixture was filtered through Celite®, and the filter cake was washed sequentially with a saturated solution of NH4Cl and EtOAc. After separation of the layers, the aqueous layer was extracted with EtOAc, and the combined organic extracts were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified by flash chromatography on silica gel eluting with 0-100% EtOAc in heptane to afford 5-(tert-butyldimethylsilyloxy)-2,2-difluoropent-3-yn-1-ol (3.3 g, 44%, light pale oil) and free propargyl alcohol 4,4-difluoropent-2-yne-1,5-diol (0.85 g 21%, clear pale oil). Silylated alcohol 5-(tert-butyldimethylsilyloxy)-2,2-difluoropent-3-yn-1-ol: 1H NMR (400 MHz, CDCl3) δ 0.14 (s, 6H), 0.92 (s. 9H), 3.88 (t, J=12.23, Hz, 2H) 4.41 (t, J=4.47, 2H); 19F NMR (376.19 MHz, CDCl3) δ −96.15 (tt, J=12.21, 4.29, 1F).

Workup

  1. filtrationthe reaction mixture was filtered through Celite®
  2. washthe filter cake was washed sequentially with a saturated solution of NH4Cl and EtOAc
  3. customAfter separation of the layers
  4. extractionthe aqueous layer was extracted with EtOAc
  5. washthe combined organic extracts were washed with brine
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash chromatography on silica gel eluting with 0-100% EtOAc in heptane

Sources & evidence

ORD record
ord-689a88606cec4653960fa10bfdbd358b
Source dataset
uspto-grants-2011_02
Patent number
US07884124B2

Reaction notes

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