Chloroform → HCID 131726705, compound

HRID 968951Notes

Reaction equation

HRID 968951 reaction equation
C([O:8][C:9]([C:11]1[CH:29]=[CH:28][C:14]2[O:15][CH2:16][CH:17]([C:19]([CH3:27])([CH3:26])[O:20][SiH2:21][C:22]([CH3:25])([CH3:24])[CH3:23])[O:18][C:13]=2[C:12]=1[CH3:30])=[O:10])C1C=CC=CC=1.[H][H].C(Cl)(Cl)Cl>C(Cl)Cl.[Pd]>[C:22]([SiH2:21][O:20][C:19]([CH3:27])([CH3:26])[CH:17]1[CH2:16][O:15][C:14]2[CH:28]=[CH:29][C:11]([C:9]([OH:10])=[O:8])=[C:12]([CH3:30])[C:13]=2[O:18]1)([CH3:25])([CH3:23])[CH3:24]

Participants

6

Reactant 3

HCID 6212ChloroformHCID 131726706HCID 131726706, compoundHCID 178418361HCID 178418361, compound2×

Product 1

HCID 131726705HCID 131726705, compoundYield 85.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6344DichloromethaneSolvent

Procedure

9.63 g of 3-(tert-Butyl-dimethyl-silanyloxymethyl)-5-methyl-2,3-dihydro-benzo[1,4]dioxine-6-carboxylic acid benzyl ester was dissolved in ca. 125 mL of dry CH2Cl2. The solution was transferred to a Parr hydrogenation bottle, and 5 g of 5% Pd on carbon were added. The bottle was charged with hydrogen and shaken on a Parr hydrogenation apparatus for 3 hours; hydrogen uptake ceased after 2 hours, as indicated by pressure monitoring. 100 mL CHCl3 were added, and the Pd/C was filtered off after adding MgSO4 as an aid to increase particle size. The CH2Cl2–CHCl3 phase was washed with 200 mL of 0.1N HCl to remove the by-product benzyl alcohol. The organic layer was dried and evaporated to give 6.47 g 3-(tert-butyl-dimethyl-silanyloxymethyl)-5-methyl-2,3-dihydro-benzo[1,4]dioxine-6-carboxylic acid, after trace solvent removal in a vacuum oven. TLC Rf=0.55 (1:1 ethyl acetate:hexane). Note: (a) Pd catalyzed hydrogenation is a far superior method to triethylsilane/palladium diacetate for this benzyl ester cleavage, (b) washing product with weak aqueous acid is a good way to remove benzyl alcohol. 1H NMR (300 MHz, CDCl3) δ (ppm): 7.55 (d, 1H), 6.7 (d, 1H), 4.3 (d, 1H), 4.17 (m, 1H), 4.02 (dd, 1H), 3.82 (dd, 1H), 3.75 (dd, 1H), (2.45 (s, 3H), 0.8 (s, 9H), 0.01 (s, 3H).

Workup

  1. additionwere added
  2. filtrationthe Pd/C was filtered off
  3. additionafter adding MgSO4 as an aid
  4. temperatureto increase particle size
  5. washThe CH2Cl2–CHCl3 phase was washed with 200 mL of 0.1N HCl
  6. customto remove the by-product benzyl alcohol
  7. customThe organic layer was dried
  8. customevaporated

Sources & evidence

ORD record
ord-6cd5d167cc474dbf82bfb7d2270cf78f
Source dataset
uspto-grants-2007_12
Patent number
US07304161B2

Reaction notes

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