Ethanol → Ethyl 4-(3-chloro-4-fluorophenyl)cyclohex-3-ene-1-carboxylate

HRID 604664Notes

Reaction equation

HRID 604664 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][C:7]=1[F:8].FC(F)(F)S(O[C:18]1[CH2:23][CH2:22][CH:21]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:20][CH:19]=1)(=O)=O.C([O-])([O-])=O.[Na+].[Na+].CCO>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.COCCOC>[Cl:1][C:2]1[CH:3]=[C:4]([C:18]2[CH2:23][CH2:22][CH:21]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:20][CH:19]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

7

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 27346603-Chloro-4-fluorophenylboronic Acid (contains varying amounts of Anhydride)HCID 9861195Ethyl 4-(((trifluoromethyl)sulfonyl)oxy)cyclohex-3-enecarboxylate

Product 1

HCID 67057759Ethyl 4-(3-chloro-4-fluorophenyl)cyclohex-3-ene-1-carboxylate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

A flask was charged with (3-chloro-4-fluorophenyl)boronic acid (495 mg, 2.84 mmol), ethyl 4-{[(trifluoromethyl)sulfonyl]oxy}cyclohex-3-ene-1-carboxylate (686 mg, 2.27 mmol), Pd(PPh3)4 (262 mg, 0.227 mmol), 1M Na2CO3 (6.81 mL, 6.81 mmol), EtOH (2.8 mL), and DME (8.6 mL). The reaction was degassed with N2, the flask was sealed, and the reaction was heated to 100° C. for 2 hours. The reaction was then cooled to room temperature and diluted with hexanes (100 mL) and EtOAc (20 mL). The mixture was washed with water (2×25 mL) and brine (2×25 mL), and the organic layer was dried (Na2SO4), filtered, and concentrated. Purification of the residue by flash chromatography on silica gel (0 to 10% EtOAc/hexanes) afforded ethyl 4-(3-chloro-4-fluorophenyl)cyclohex-3-ene-1-carboxylate. Rf=0.25 (5% EtOAc/hexanes). 1H NMR (500 MHz, CDCl3): δ 7.37 (dd, J=7.1, 2.3 Hz, 1H), 7.20 (m, 1H), 7.05 (t, J=8.8 Hz, 1H), 6.05 (s, 1H), 4.16 (q, J=7.1 Hz, 2H), 2.36-2.62 (m, 4H), 2.17 (m, 1H), 1.84 (m, 1H), 1.27 (t, J=7.1 Hz, 3H).

Workup

  1. customThe reaction was degassed with N2
  2. customthe flask was sealed
  3. temperatureThe reaction was then cooled to room temperature
  4. additiondiluted with hexanes (100 mL) and EtOAc (20 mL)
  5. washThe mixture was washed with water (2×25 mL) and brine (2×25 mL)
  6. dry with materialthe organic layer was dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification of the residue by flash chromatography on silica gel (0 to 10% EtOAc/hexanes)

Sources & evidence

ORD record
ord-f6677d842e124786ba74d6d5dd1108d5
Source dataset
uspto-grants-2011_03
Patent number
US07910592B2

Reaction notes

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