Styrene → HCID 10613244, compound

HRID 842645Notes

Reaction equation

HRID 842645 reaction equation
ClC1[CH:7]=[CH:6][C:5]([OH:8])=C(F)C=1.[Cl:10][C:11]1[C:16]([CH:17]=O)=[C:15]([F:19])[C:14]([O:20][CH2:21][CH3:22])=[CH:13][CH:12]=1.ClC1C(C=C)=C(F)[C:27]([O:33]CC)=[CH:26]C=1.C=CC1C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>ClC(Cl)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:27]([O:33][C:5]([C@@H:6]1[CH2:7][C@@H:17]1[C:16]1[C:11]([Cl:10])=[CH:12][CH:13]=[C:14]([O:20][CH2:21][CH3:22])[C:15]=1[F:19])=[O:8])[CH3:26]

Participants

8

Reactant 5

HCID 7501StyreneHCID 1819754-Chloro-2-fluorophenolHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 104883476-Chloro-3-ethoxy-2-fluorobenzaldehydeHCID 10798114HCID 10798114, compound

Product 1

HCID 10613244HCID 10613244, compoundYield 10%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 63651,1-DichloroethaneSolvent2×

Procedure

The titled compound was obtained starting from 4-chloro-2-fluorophenol which was converted to 6-chloro-3-ethoxy-2-fluorobenzaldehyde according to procedure in Example 362 of WO 93/03022. This aldehyde was converted to 6-chloro-3-ethoxy-2-fluorostyrene according to procedure in Example 375 of WO 93/03022. Styrene (30.7 g, 153 mmole) was dissolved in dichloroethane (400 mL) and CuJ (50 mg) and Pd(OAc)2 (50 mg) added. The temperature of this solution was raised to reflux and diethyl azodicarboxylate (32.2 mL, 306 mmole) in 100 mL of dichloroethane was dropped into it during a period of 2 hrs. The reflux was continued for 1 hr. The reaction mixture was evaporated and the residue purified by chromatography on silica gel column EtOAc/Hexane 2:98-5:95 as eluent to give 4.36 g (10%) of pure (+,−)-cis-2-(6-chloro-3-ethoxy-2-fluorophenyl)-cyclopropylcarboxylic acid ethyl ester which was then hydrolyzed in KOH (2.56 g)—EtOH/H2O (45 mL/5mL) at 100° C. for 24 hrs. The reaction mixture was extracted twice with hexane, made acidic with conc. HCl and extracted with diethyl ether which was dried over Na2SO4 and evaporated to give 3.87 g (98%) of pure acid.

Workup

  1. temperatureThe temperature of this solution was raised
  2. temperatureto reflux
  3. customThe reaction mixture was evaporated
  4. customthe residue purified by chromatography on silica gel column EtOAc/Hexane 2:98-5:95 as eluent

Sources & evidence

ORD record
ord-948f066a1af64023a5aee3e223bb777f
Source dataset
uspto-grants-2002_04
Patent number
US06376492B1

Reaction notes

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