Ethyl Acetate → HCID 21070521, compound

HRID 1371732Notes

Reaction equation

HRID 1371732 reaction equation
[C:1]([Si:5]([CH3:28])([CH3:27])[O:6][C:7]1[C:8]([O:25][CH3:26])=[C:9]([CH:15]([C:17]2[C:18]([Cl:24])=[N:19][C:20]([Cl:23])=[N:21][CH:22]=2)[OH:16])[C:10]([F:14])=[C:11]([F:13])[CH:12]=1)([CH3:4])([CH3:3])[CH3:2].C(=O)(O)[O-].[Na+].Cl[O-].[Na+].C(OCC)(=O)C>C(Cl)Cl.O.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CC1(C)N([O])C(C)(C)CCC1>[C:1]([Si:5]([CH3:28])([CH3:27])[O:6][C:7]1[C:8]([O:25][CH3:26])=[C:9]([C:15]([C:17]2[C:18]([Cl:24])=[N:19][C:20]([Cl:23])=[N:21][CH:22]=2)=[O:16])[C:10]([F:14])=[C:11]([F:13])[CH:12]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 21070520HCID 21070520, compoundHCID 23665760Sodium Hypochlorite3×

Product 1

HCID 21070521HCID 21070521, compoundYield 96%

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 2724126TempoCatalystHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of [3-(tert-butyl-dimethyl-silanyloxy)-5,6-difluoro-2-methoxy-phenyl]-(2,4-dichloro-pyrimidin-5-yl)-methanol (955 mg, 2.116 mmol, Example 267) in methylene chloride (6 mL) and water (1 mL) were added sodium bicarbonate (80 mg, 0.952 mmol), tetrabutylammonium bromide (21 mg, 0.0635 mmol), TEMPO (3.3 mg, 0.0212 mmol, Aldrich). The mixture was cooled to 0° C. and sodium hypochlorite (2.548 mL, 2.539 mmol, Clorox™) was added. The reaction mixture was stirred at 0° C. for 30 minutes and more sodium hypochlorite (0.5 mL) was added. Thin layer chromatography (silica gel, 10% ethyl acetate in hexanes) still showed the alcohol starting material. More sodium hypochlorite (3×0.5 mL) was added until no alcohol was seen. The reaction mixture was diluted with methylene chloride (30 mL) and water (20 mL). The layers were separated, and the organic phase was washed with water (2×10 mL), brine (1×10 mL) and dried over anhydrous magnesium sulfate. The solids were filtered off and the filtrate was concentrated in vacuo to give [3-(tert-butyl-dimethyl-silanyloxy)-5,6-difluoro-2-methoxy-phenyl]-(2,4-dichloro-pyrimidin-5-yl)-methanone as pale yellow oil (910 mg, 96%). The crude product was used without further purification.

Workup

  1. customThe layers were separated
  2. washthe organic phase was washed with water (2×10 mL), brine (1×10 mL)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationThe solids were filtered off
  5. concentrationthe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-4e8ac89000a744a5af0317f39cce51d2
Source dataset
uspto-grants-2007_01
Patent number
US07157455B2

Reaction notes

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