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

HRID 2103075Notes

Reaction equation

HRID 2103075 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[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:19][C:20]1[CH:25]=[CH:24][C:23](I)=[CH:22][CH:21]=1.CC([O-])(C)C.[Na+]>>[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([N:9]2[C:10]3[C:5](=[CH:4][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:22][CH:21]=1

Participants

4

Reactant 3

HCID 125101-Chloro-4-iodobenzeneHCID 23676156Sodium t-butoxideHCID 69055426HCID 69055426, compound

Product 1

HCID 690567811'-(4-chlorophenyl)-6'-methoxy-7',8'-dimethyl-1'H-spiro[cyclobutane-1,3'-quinolin]-4'(2'H)-oneYield 65.5%

Conditions

Temperature
105 °C

Procedure

6′-Methoxy-7′,8′-dimethyl-1′H-spiro[cyclobutane-1,3′-quinolin]-4′(2′H)-one (300 mg) was mixed with 1-chloro-4-iodobenzene (465 mg), NaOtBu (187.4 mg) and [PdBr(tBu3P)2]2 (20 mg). The reaction tube was then sealed with rubber septum, the air was evacuated, then it was flushed with nitrogen. This process was repeated three times, and then toluene (1.5 mL) was added. The reaction tube was then heated in a 105° C. bath for 2 hours. The mixture was then cooled, quenched with water, and extracted with EtOAc. The organic phase was washed with brine, dried and evaporated to give a crude mixture, that was eluted on a silica column (Hexane: EtOAc; 10:1.5-10:2) to give 1′-(4-chlorophenyl)-6′-methoxy-7′,8′-dimethyl-1′H-spiro[cyclobutane-1,3′-quinolin]-4′(2′H)-one (285 mg) as a yellow solid. 1H-NMR (300 MHz, CDCl3) δ=7.399 (s, 1H), 7.16-7.09 (m, 2H), 6.81-6.73 (m, 2H), 4.07 (s, 2H), 3.86 (s, 3H), 2.36-2.23 (m, 2H), 2.13 (s, 3H), 1.99-1.78 (m, 1H), 1.76 (s, 3H), 1.69-1.42 (m, 3H) ppm. 13C-NMR (75 MHz, CDCl3) δ=198.29, 154.39, 149.44, 141.4, 134.46, 132.07, 129.25, 125.87, 124.07, 121.47, 105.15, 60.96, 55.62, 48.86, 28.59, 15.55, 15.52, and 13.09 ppm.

Workup

  1. customThe reaction tube was then sealed with rubber septum
  2. customthe air was evacuated
  3. customit was flushed with nitrogen
  4. additiontoluene (1.5 mL) was added
  5. temperatureThe mixture was then cooled
  6. customquenched with water
  7. extractionextracted with EtOAc
  8. washThe organic phase was washed with brine
  9. customdried
  10. customevaporated
  11. customto give a crude mixture, that
  12. washwas eluted on a silica column (Hexane: EtOAc; 10:1.5-10:2)

Sources & evidence

ORD record
ord-d50e6b781abc42bdbf759e40400918b5
Source dataset
uspto-grants-2009_08
Patent number
US07576094B2

Reaction notes

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