1-Chloro-4-iodobenzene → 1'-(4-chlorophenyl)-6'-methoxy-5',7',8'-trimethyl-1'H-spiro[cyclobutane-1,3'-quinolin]-4'(2'H)-one

HRID 2103065Notes

Reaction equation

HRID 2103065 reaction equation
[CH3:1][O:2][C:3]1[C:4]([CH3:19])=[C:5]2[C:10](=[C:11]([CH3:14])[C:12]=1[CH3:13])[NH:9][CH2:8][C:7]1([CH2:17][CH2:16][CH2:15]1)[C:6]2=[O:18].[Cl:20][C:21]1[CH:26]=[CH:25][C:24](I)=[CH:23][CH:22]=1.O(C(C)(C)C)[Na].C(P)(C)(C)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCOC(C)=O.CCCCCC>[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([N:9]2[C:10]3[C:5](=[C:4]([CH3:19])[C:3]([O:2][CH3:1])=[C:12]([CH3:13])[C:11]=3[CH3:14])[C:6](=[O:18])[C:7]3([CH2:15][CH2:16][CH2:17]3)[CH2:8]2)=[CH:23][CH:22]=1

Participants

7

Reactant 4

HCID 125101-Chloro-4-iodobenzeneHCID 123165tert-ButylphosphineHCID 690523766'-Methoxy-5',7',8'-trimethyl-1'H-spiro[cyclobutane-1,3'-quinolin]-4'(2'H)-oneHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 690567921'-(4-chlorophenyl)-6'-methoxy-5',7',8'-trimethyl-1'H-spiro[cyclobutane-1,3'-quinolin]-4'(2'H)-oneYield 65.8%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
120 °C

Procedure

6′-Methoxy-5′,7′,8′-trimethyl-1′H-spiro[cyclobutane-1,3′-quinolin]-4′(2′H)-one (146.7 mg), palladium (II) acetate, 1-chloro-4-iodobenzene (202.5 mg) and NaO-t-Bu (81.6 mg) were added to an oven dried tube. The flask was capped and the air evacuated with a house vacuum line, then refilled with nitrogen. This nitrogen flushing was repeated 3 times. Toluene (1.5 mL) was then added and the suspension was stirred for 15 min at room temperature before ter-butylphosphine (1.7 mL, 0.056 mmol, 33.7 mM in toluene) was added. The mixture was then heated up in oil bath (120° C.) for 2.5 h. It was then quenched with water and extracted with ethylacetate. The organic phase was washed with brine, dried and evaporated to give an oil, which was passed through a silica column (EtOAc/Hexane: 0-10%) to give 1′-(4-chlorophenyl)-6′-methoxy-5′,7′,8′-trimethyl-1′H-spiro[cyclobutane-1,3′-quinolin]-4′(2′H)-one (137.6 mg) as a solid. 1H-NMR (300 MHz, CDCl3) δ=7.257-7.026 (d, 2H), 6.904-6.553 (d, 2H), 4.09 (s, 2H), 3.71 (s, 3H), 2.62 (s, 3H), 2.454-2.276 (m, 2H), 2.24 (s, 3H), 2.125-1.836 (m, 2H), 1.81 (s, 3H), 1.746-1.554 (m, 2H) ppm. 13CNMR (75 MHz, CDCl3) δ=201.17, 148.99, 144.28, 137.51, 131.65, 129.92, 129.28, 125.56, 125.37, 121.03, 60.28, 60.04, 50.71, 9.71, 15.57, 15.44, 14.63, 13.92 ppm.

Workup

  1. customdried tube
  2. customThe flask was capped
  3. customthe air evacuated with a house vacuum line
  4. additionrefilled with nitrogen
  5. additionToluene (1.5 mL) was then added
  6. additionwas added
  7. customIt was then quenched with water
  8. extractionextracted with ethylacetate
  9. washThe organic phase was washed with brine
  10. customdried
  11. customevaporated
  12. customto give an oil, which

Sources & evidence

ORD record
ord-1ddd876489d24886b21a4810c4195b98
Source dataset
uspto-grants-2009_08
Patent number
US07576094B2

Reaction notes

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