2,2-Dimethoxypropane → (6-fluoro-2,2-dimethyl-4H-1,3-benzodioxin-8-yl)methanol

HRID 253275Notes

Reaction equation

HRID 253275 reaction equation
[CH3:1][C:2]1(C)[C@]2(CS(O)(=O)=O)C(C[CH:3]1CC2)=O.[F:16][C:17]1[CH:22]=[C:21]([CH2:23][OH:24])[C:20]([OH:25])=[C:19]([CH2:26][OH:27])[CH:18]=1.COC(OC)(C)C.C([O-])(O)=O.[Na+]>CC(C)=O.C(OCC)(=O)C>[F:16][C:17]1[CH:18]=[C:19]([CH2:26][OH:27])[C:20]2[O:25][C:2]([CH3:3])([CH3:1])[O:24][CH2:23][C:21]=2[CH:22]=1

Participants

7

Reactant 4

HCID 64952,2-DimethoxypropaneHCID 218580(1S)-(+)-Camphor-10-sulphonic acidHCID 516892Sodium BicarbonateHCID 23935454-Fluoro-2,6-bis(hydroxymethyl)phenol

Product 1

HCID 66890263(6-fluoro-2,2-dimethyl-4H-1,3-benzodioxin-8-yl)methanolYield 91%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
55 °C

Procedure

D(+)-10-Camphorsulfonic acid (5.1 g, 22 mmol), 4-fluoro-2,6-bis(hydroxymethyl)phenol (74.5 g, 432 mmol), and 2,2-dimethoxypropane (90 mL, 734 mmol) were dissolved in acetone. To the solution was added 45 g of 4 Å molecular sieves. The resulting suspension was heated to 55° C. for 1 h and then cooled to rt. The mixture was neutralized with aqueous NaHCO3 (sat) and diluted with ethyl acetate. Solids were removed by filtration. The solvent volume was reduced in vacuo. Ethyl acetate and aqueous NaHCO3 (sat) were added, and the layers were partitioned. The organic phase was washed with brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. Crude (6-fluoro-2,2-dimethyl-4H-1,3-benzodioxin-8-yl)methanol was isolated as an orange oil (91.7 g, 432 mmol, 100%). (17.2 g, 86.6 mmol, 91% yield). 1H NMR (400 MHz, CDCl3): δ 7.01 (dd, 1H), 6.79 (dd, 1H), 5.20 (t, 1H), 4.77 (s, 2H), 4.40 (d, 2H), 1.42 (s, 6H); GCMS for C11H13FO3: 212 (M+)

Workup

  1. additionTo the solution was added 45 g of 4 Å molecular sieves
  2. temperaturecooled to rt
  3. customSolids were removed by filtration
  4. additionEthyl acetate and aqueous NaHCO3 (sat) were added
  5. customthe layers were partitioned
  6. washThe organic phase was washed with brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7c1155fd97d6431788c8656fc35576ec
Source dataset
uspto-grants-2011_01
Patent number
US07872014B2

Reaction notes

Loading…