Boron tribromide → 1'-(4-Chlorophenyl)-5',7',8'-trimethyl-1',4'-dihydro-2'H-spiro[cyclobutane-1,3'-quinolin]-6'-ol

HRID 2103068Notes

Reaction equation

HRID 2103068 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:17]3[C:12](=[C:13]([CH3:22])[C:14]([O:20]C)=[C:15]([CH3:19])[C:16]=3[CH3:18])[CH2:11][C:10]3([CH2:25][CH2:24][CH2:23]3)[CH2:9]2)=[CH:4][CH:3]=1.B(Br)(Br)Br>ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:17]3[C:12](=[C:13]([CH3:22])[C:14]([OH:20])=[C:15]([CH3:19])[C:16]=3[CH3:18])[CH2:11][C:10]3([CH2:25][CH2:24][CH2:23]3)[CH2:9]2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 690532931'-(4-chlorophenyl)-6'-methoxy-5',7',8'-trimethyl-2',4'-dihydro-1'H-spiro[cyclobutane-1,3'-quinoline]

Product 1

HCID 116242921'-(4-Chlorophenyl)-5',7',8'-trimethyl-1',4'-dihydro-2'H-spiro[cyclobutane-1,3'-quinolin]-6'-olYield 89.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

1′-(4-chlorophenyl)-6′-methoxy-5′,7′,8′-trimethyl-2′,4′-dihydro-1′H-spiro[cyclobutane-1,3′-quinoline] (200 mg) was dissolved in dichloromethane (15 mL) cooled in a bath (−78° C.). To this solution was added BBr3 (4 mL, 1 M in dichloromethane). The temperature was then raised to 10° C. After another 1.5 h, the mixture was quenched with 3 mL saturated NaHCO3, and extracted with ethylacetate. The organic phase was washed with brine, dried and evaporated to an oil, which was passed through a silica column (EtOAc in Hexane: 5-16% in 30 min) to give 1′-(4-chlorophenyl)-5′,7′,8′-trimethyl-2′,4′-dihydro-1′H-spiro[cyclobutane-1,3′-quinolin]-6′-ol (172 mg) as an off-while oil. 1H-NMR (300 MHz, CDCl3): δ=7.18-6.94 (d, 2H), 6.74-6.54 (d, 2H), 4.54 (s, 1H), 3.63 (s, 2H), 2.72 (s, 2H), 2.19 (s, 3H), 2.13 (s, 3H), 1.79 (s, 3H), 1.97-1.54 (m, 6H) ppm. 13C-NMR (75 MHz, CDCl3) δ=150.31, 148.19, 134.19, 129.01, 128.71, 128.23, 123.3, 120.69, 119.34, 119.25, 60.83, 40.61, 38.49, 32.91, 15.82, 15.56, 12.6, 11.57 ppm.

Workup

  1. temperatureThe temperature was then raised to 10° C
  2. customthe mixture was quenched with 3 mL saturated NaHCO3
  3. extractionextracted with ethylacetate
  4. washThe organic phase was washed with brine
  5. customdried
  6. customevaporated to an oil, which
  7. customwas passed through a silica column (EtOAc in Hexane: 5-16% in 30 min)

Sources & evidence

ORD record
ord-e1f632213a0a4885bed9e126593cdd6f
Source dataset
uspto-grants-2009_08
Patent number
US07576094B2

Reaction notes

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