Ammonium Hydroxide → 4-(4-Chloro-2-{[(triisopropylsilyl)oxy]methyl}phenyl)azetidin-2-one

HRID 1058258Notes

Reaction equation

HRID 1058258 reaction equation
C([Li])CCC.[Cl:6][C:7]1[CH:8]=[CH:9][C:10](I)=[C:11]([CH:24]=1)[CH2:12][O:13][Si:14]([CH:21]([CH3:23])[CH3:22])([CH:18]([CH3:20])[CH3:19])[CH:15]([CH3:17])[CH3:16].C(O[CH:30]1[NH:33][C:32](=[O:34])[CH2:31]1)(=O)C.[Cl-].[NH4+].[OH-].[NH4+]>CCOCC.CSC.C1COCC1>[Cl:6][C:7]1[CH:8]=[CH:9][C:10]([CH:30]2[NH:33][C:32](=[O:34])[CH2:31]2)=[C:11]([CH2:12][O:13][Si:14]([CH:21]([CH3:23])[CH3:22])([CH:18]([CH3:20])[CH3:19])[CH:15]([CH3:17])[CH3:16])[CH:24]=1

Participants

9

Reactant 5

HCID 14923Ammonium HydroxideHCID 25517Ammonium ChlorideHCID 1199814-Acetoxy-2-azetidinoneHCID 186723614-Chloro-1-iodo-2-[[[tris(1-methylethyl)silyl]oxy]methyl]benzeneHCID 178418339Butyllithium

Product 1

HCID 186723524-(4-Chloro-2-{[(triisopropylsilyl)oxy]methyl}phenyl)azetidin-2-oneYield 86%

Reagents, catalysts & solvents 3

HCID 1068Dimethyl SulfideSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-50 °C

Procedure

n-Butyl-lithium (2.5 M solution in hexanes, 3.6 mL) was added to stirred solution of [(5-chloro-2-iodobenzyl)oxy](triisopropyl)silane (3.82 g, 9.0 mmol) in ether (18 mL) at −78° C. under nitrogen. After 10 min a solution of copper(I) bromide-dimethylsulfide complex (0.925 g, 4.5 mmol) in dimethylsulfide (36 mL) was added and the solution was warmed to −50° C. A solution of 4-acetoxy-2-azetidinone (0.291 g, 2.25 mmol) in THF (2 mL) was added and the solution was warmed to −30° C. After a further 1 h the reaction was poured into 10% ammonium chloride solution basicified with ammonium hydroxide and extracted into ether. The organic layer was dried (Na2SO4) and evaporated in vacuo to an oil which was purified by flash column chromatography on silica (eluting with 5% methylene chloride/0-50% ethyl acetate/hexanes gradient) to give 4-(4-chloro-2-{[(triisopropylsilyl)oxy]methyl}phenyl)azetidin-2-one (0.712 g) as a heavy oil: 1H NMR (CDCl3, 400 MHz) δ 1.08 (d, J=6.4 Hz, 18H), 1.16 (septet, J=6.4 Hz, 3H), 2.78 (dd, J=2.6, 14.8 Hz, 1H), 3.45 (dq, J=14.8, 2.6 Hz, 1H), 4.72 (d, J=13.1 Hz, 1H), 4.78 (d, J=13.1 Hz, 1H), 4.94 (q, J=2.6 Hz, 1H), 6.06 (br s, 1H), 7.30 (dd, J=2.1, 8.4 Hz, 1H), 7.43 (m, 2H).

Workup

  1. temperaturethe solution was warmed to −30° C
  2. extractionextracted into ether
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. customevaporated in vacuo to an oil which
  5. customwas purified by flash column chromatography on silica (eluting with 5% methylene chloride/0-50% ethyl acetate/hexanes gradient)

Sources & evidence

ORD record
ord-9b343139991e417b97e35ba684dcb4dc
Source dataset
uspto-grants-2003_02
Patent number
US06515011B2

Reaction notes

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