Pyridine → 7-(acetylamino)-4-bromo-9a-butyl-8-chloro-6-fluoro-1,2,9,9a-tetrahydro-3H-fluoren-3-one

HRID 1372508Notes

Reaction equation

HRID 1372508 reaction equation
[NH2:1][C:2]1[C:14]([Cl:15])=[C:13]2[C:5]([C:6]3[C:11]([CH2:16][CH2:17][CH2:18][CH3:19])([CH2:12]2)[CH2:10][CH2:9][C:8](=[O:20])[C:7]=3[Br:21])=[CH:4][C:3]=1[F:22].N1C=CC=CC=1.[C:29](Cl)(=[O:31])[CH3:30].[OH-].[Na+]>C(Cl)Cl.N1C=CC=CC=1.C(Cl)(=O)C.CCO>[C:29]([NH:1][C:2]1[C:14]([Cl:15])=[C:13]2[C:5]([C:6]3[C:11]([CH2:16][CH2:17][CH2:18][CH3:19])([CH2:12]2)[CH2:10][CH2:9][C:8](=[O:20])[C:7]=3[Br:21])=[CH:4][C:3]=1[F:22])(=[O:31])[CH3:30]

Participants

9

Reactant 4

HCID 1049PyridineHCID 6367Acetyl chlorideHCID 14798Sodium HydroxideHCID 102217817-amino-4-bromo-9a-butyl-8-chloro-6-fluoro-1,2,9,9a-tetrahydro-3H-fluoren-3-one

Product 1

HCID 210720087-(acetylamino)-4-bromo-9a-butyl-8-chloro-6-fluoro-1,2,9,9a-tetrahydro-3H-fluoren-3-oneYield 98%

Reagents, catalysts & solvents 4

HCID 1049PyridineCatalystHCID 6367Acetyl chlorideCatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

A partial solution of 7-amino-4-bromo-9a-butyl-8-chloro-6-fluoro-1,2,9,9a-tetrahydro-3H-fluoren-3-one (0.940 g, 2.44 mmol) in CH2Cl2 (7.5 mL) was cooled in an ice bath and treated successively with pyridine (0.202 mL, 2.5 mmol) and acetyl chloride (0.178 mL, 2.5 mmol). The reaction mixture was placed under a N2 atmosphere and stirred at room temperature. Additional pyridine (0.01 mL, 0.12 mmol and 0.039 mL, 0.48 mmol) was added after 4 and 5 hours, respectively; and additional acetyl chloride (0.009 mL, 0.12 mmol; 0.035 mL, 0.49 mmol; and 0.175 mL, 2.45 mmol) was added after 4, 5, and 5.5 hours, respectively. After stirring overnight at room temperature, the mixture was treated with EtOH (10 mL) and 5N NaOH (ca. 1 mL), stirred briefly, and then partitioned between EtOAc and water. The organic phase was washed with brine, dried over MgSO4, filtered, and evaporated under vacuum to provide 7-(acetylamino)-4-bromo-9a-butyl-8-chloro-6-fluoro-1,2,9,9a-tetrahydro-3H-fluoren-3-one (1.02 g, 98%) as an orange solid.

Workup

  1. stirringAfter stirring overnight at room temperature
  2. stirringstirred briefly
  3. custompartitioned between EtOAc and water
  4. washThe organic phase was washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated under vacuum

Sources & evidence

ORD record
ord-eebf10404c984e91af6beb4e88fefc99
Source dataset
uspto-grants-2007_01
Patent number
US07157604B2

Reaction notes

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