tert-Butyl acetate → Lithium Hexamethyldisilazide

HRID 1167811Notes

Reaction equation

HRID 1167811 reaction equation
[Li:1]CCCC.[CH3:6][Si:7]([NH:10][Si:11]([CH3:14])([CH3:13])[CH3:12])([CH3:9])[CH3:8].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.[C:43]([O:47][C:48](=[O:50])[CH3:49])([CH3:46])([CH3:45])[CH3:44].[Cl:51][C:52]1[CH:53]=[C:54]([C:59]([F:62])([F:61])[F:60])[CH:55]=[CH:56][C:57]=1I>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Li+:1].[CH3:6][Si:7]([N-:10][Si:11]([CH3:14])([CH3:13])[CH3:12])([CH3:9])[CH3:8].[C:43]([O:47][C:48](=[O:50])[CH2:49][C:57]1[CH:56]=[CH:55][C:54]([C:59]([F:62])([F:61])[F:60])=[CH:53][C:52]=1[Cl:51])([CH3:46])([CH3:45])[CH3:44]

Participants

9

Reactant 5

HCID 10908tert-Butyl acetateHCID 13838HexamethyldisilazaneHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 27366123-Chloro-4-iodobenzotrifluorideHCID 178418339Butyllithium

Product 2

HCID 2733832Lithium HexamethyldisilazideHCID 12088184HCID 12088184, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
10 °C

Procedure

A solution of LiHMDS in toluene was prepared by the addition of n-BuLi (357 mL of a 1.6 M solution in hexanes, 571 mmol) to a cold (−78° C.) solution of HMDS (120.5 mL, 571 mmol) in toluene (700 mL). After 30 min, the reaction mixture was allowed to warm up to 10° C. over 1 h. The solution was then transferred via a cannula to a flame-dried, three-neck flask under N2 containing Pd2dba3 (4.18 g, 4.57 mmol) and (2′-dicyclohexylphosphanylbiphenyl-2-yl)-dimethylamine (3.77 g, 9.59 mmol). The mixture was stirred for 15 min at 15° C., cooled to −10° C. and t-butylacetate (70.5 mL, 525.4 mmol) was added dropwise. After 10 min, 3-chloro-4-iodobenzotrifluoride (70 g, 228.4 mmol) was added and the reaction mixture was warmed up to 28° C. After stirring at this temperature for 1.5 h, the mixture was filtered through silica gel, using toluene as eluent, and the solvent was removed in vacuo. The residue was purified using flash chromatography (silica gel, 98:2 hexanes:EtOAc) to yield (2-chloro-4-trifluoromethylphenyl)-acetic acid tert-butyl ester as a solid.

Workup

  1. temperaturecooled to −10° C.
  2. waitAfter 10 min
  3. temperaturethe reaction mixture was warmed up to 28° C
  4. stirringAfter stirring at this temperature for 1.5 h
  5. filtrationthe mixture was filtered through silica gel
  6. customthe solvent was removed in vacuo
  7. customThe residue was purified

Sources & evidence

ORD record
ord-0bf8cd37211f48f0bde81966ad92368b
Source dataset
uspto-grants-2003_09
Patent number
US06620838B1

Reaction notes

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