Tetrahydrofuran → (+)-(4aR)-(10bR)-4-methyl-8-[2,8-bis(trifluoromethyl)-4-quinolinyl]-10b-methyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]-quinolin-3-one

HRID 1379536Notes

Reaction equation

HRID 1379536 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]1[CH:12]=[C:11](Br)[C:10]2[C:5](=[C:6]([C:14]([F:17])([F:16])[F:15])[CH:7]=[CH:8][CH:9]=2)[N:4]=1.[C:20](=[O:23])([O-])[O-].[Na+].[Na+].[CH2:26]1[CH2:30]O[CH2:28][CH2:27]1>C(OCC)(=O)C.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>[CH3:5][N:4]1[C@H:3]2[C@@:26]([CH3:30])([C:26]3[CH:30]=[CH:14][C:6]([C:11]4[C:10]5[C:5](=[C:6]([C:14]([F:17])([F:16])[F:15])[CH:7]=[CH:8][CH:9]=5)[N:4]=[C:3]([C:2]([F:19])([F:18])[F:1])[CH:12]=4)=[CH:7][C:27]=3[CH2:28][CH2:2]2)[CH2:27][CH2:28][C:20]1=[O:23]

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 10340Sodium CarbonateHCID 40712424-Bromo-2,8-bis(trifluoromethyl)quinoline

Product 1

HCID 54475496(+)-(4aR)-(10bR)-4-methyl-8-[2,8-bis(trifluoromethyl)-4-quinolinyl]-10b-methyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]-quinolin-3-oneYield 48%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A 15 mL round bottom flask was charged with (+)-(4aR)-(10bR)-4-methyl-10b-methyl-1,2,3,4,4a-,5,6,10b-octahydrobenzo[f]quinolin-3-one-8-boronic acid (178 mg, 0.65 mmol), tetrakis(triphenylphosphine)palladium(0) (23 mg, 0.02 mmol), 2,8-bis(trifluoromethyl)-4-bromoquinoline (224 mg, 0.65 mmol), 0.65 mL of 2M aqueous sodium carbonate and 2 mL of THF, fitted with a reflux condenser, and the stirred mixture was heated at 80°, under nitrogen, for 24 h. The mixture was cooled, diluted with ethyl acetate (75 mL) and washed with brine (2×25 mL). The combined organic extracts were dried over sodium sulfate, concentrated, and purified by silica gel chromatography (ethyl acetate eluent) to give 153 mg (48%) of the title compound as an amorphous foam. mp 100°-106°. FDMS: m/e=492. α[D]589 =+51.86 (c=0.47, chloroform)

Workup

  1. customfitted with a reflux condenser
  2. temperaturethe stirred mixture was heated at 80°, under nitrogen, for 24 h
  3. temperatureThe mixture was cooled
  4. washwashed with brine (2×25 mL)
  5. dry with materialThe combined organic extracts were dried over sodium sulfate
  6. concentrationconcentrated
  7. custompurified by silica gel chromatography (ethyl acetate eluent)

Sources & evidence

ORD record
ord-f84442b0a3364939becea72afe301fcb
Source dataset
uspto-grants-1997_09
Patent number
US05670514

Reaction notes

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