Sodium Carbonate → (+)-(4aR)-(10bR)-4-methyl-8-(3,4-difluorophenyl)-10b-methyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolin-3-one

HRID 1682788Notes

Reaction equation

HRID 1682788 reaction equation
[CH3:1][N:2]1[C@H:11]2[C@@:6]([CH3:17])([C:7]3[CH:15]=[CH:14][C:13](Br)=[CH:12][C:8]=3[CH2:9][CH2:10]2)[CH2:5][CH2:4][C:3]1=[O:18].[F:19][C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[CH:24][C:25]=1[F:26].C(=O)([O-])[O-].[Na+].[Na+].B(O)O>C(Cl)(Cl)Cl.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd].C1COCC1>[CH3:1][N:2]1[C@H:11]2[C@@:6]([CH3:17])([C:7]3[CH:15]=[CH:14][C:13]([C:23]4[CH:22]=[CH:21][C:20]([F:19])=[C:25]([F:26])[CH:24]=4)=[CH:12][C:8]=3[CH2:9][CH2:10]2)[CH2:5][CH2:4][C:3]1=[O:18]

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 61668Boronic AcidHCID 27343373,4-Difluorobenzeneboronic acidHCID 15355317(4aR)-(10bR)-4,10b-dimethyl-8-bromo-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolin-3-one

Product 1

HCID 53752140(+)-(4aR)-(10bR)-4-methyl-8-(3,4-difluorophenyl)-10b-methyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolin-3-oneYield 58.6%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Procedure

A 15 mL round bottom flask was charged with (+)-(4aR)-(10bR)-4-methyl-8-bromo-10b-methyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolin-3-one (200 mg, 0.65 mmol), tetrakis(triphenylphosphine) palladium (0) (23 mg, 0.02 mmol), 3,4-difluorophenylboronic acid (123 mg, 0.78 mmol),0.65 mL of 2M sodium carbonate solution and 2 mL of THF, fitted with a reflux condenser, and the stirred mixture was heated at 80°, under nitrogen, for 24 h. Additional palladium reagent and boronic acid was added, and the mixture was heated for an additional 24 h. The mixture was cooled, diluted with chloroform (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 130 mg (58%) of the title compound as a white solid. mp 143-148°. FDMS: m/e =341 α[D]589 =+65.12 (c=0.97, 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 heated for an additional 24 h
  4. temperatureThe mixture was cooled
  5. washwashed with brine (2×25 mL)
  6. dry with materialThe combined organic extracts were dried over sodium sulfate
  7. concentrationconcentrated
  8. custompurified by silica gel chromatography (ethyl acetate eluent)

Sources & evidence

ORD record
ord-9bccdf5397ea4074933c8a39be06d6bd
Source dataset
uspto-grants-1997_06
Patent number
US05635197

Reaction notes

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