N-bromobutanimide → HCID 10091641, compound

HRID 2113675Notes

Reaction equation

HRID 2113675 reaction equation
[CH2:1]([C:5]12[CH2:21][C:20](=[O:22])[CH:19]=[C:6]1[C:7]1[C:12]([CH2:13][CH2:14]2)=[C:11]([Cl:15])[C:10]([O:16]C)=[C:9]([F:18])[CH:8]=1)[CH2:2][CH2:3][CH3:4].[Br:23]N1C(=O)CCC1=O.[Cl-].[Li+]>CN(C=O)C>[Br:23][C:19]1[C:20](=[O:22])[CH2:21][C:5]2([CH2:1][CH2:2][CH2:3][CH3:4])[CH2:14][CH2:13][C:12]3[C:7](=[CH:8][C:9]([F:18])=[C:10]([OH:16])[C:11]=3[Cl:15])[C:6]=12

Participants

5

Reactant 3

HCID 67184N-bromobutanimideHCID 433294Lithium ChlorideHCID 58604048HCID 58604048, compound

Product 1

HCID 10091641HCID 10091641, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

A solution of 3a-butyl-6-chloro-8-fluoro-7-methoxy-3,3a,4,5-tetrahydro-cyclopenta[a]naphthalen-2-one (22 mg, 0.07 mmol) in DMF (0.12 mL) was treated with N-bromosuccinimide (12 mg, 0.07 mmol) at room temperature under N2 for 100 minutes, after which very little reaction had occurred. The reaction was thus heated to 60° C. for 50 minutes, then diluted with DMF (0.5 mL). Lithium chloride (29 mg, 0.68 mmol) was added and the reaction was heated to 100° C. After stirring at 100° C. for 1.5 hours the reaction was heated at 120° C. for 50 minutes. The reaction was cooled to room temperature and then partitioned between EtOAc/H2O. The organic portion was washed several times with water, then with brine, dried over MgSO4, filtered and then concentrated under vacuum. The crude material was purified by preparative layer chromatography on a 0.05×20×20 cm silica gel GF plate (Analtech, Newark, Del.), developing with 2.5% MeOH in CH2Cl2. The low Rf band was eluted with 5% MeOH in CH2Cl2 and concentrated under vacuum to give 1-bromo-3a-butyl-6-chloro-8-fluoro-7-hydroxy-3,3a,4,5-tetrahydro-2H-cyclopenta[a]naphthalen-2-one as an off-white film.

Workup

  1. customafter which very little reaction
  2. temperaturethe reaction was heated to 100° C
  3. temperaturewas heated at 120° C. for 50 minutes
  4. temperatureThe reaction was cooled to room temperature
  5. custompartitioned between EtOAc/H2O
  6. washThe organic portion was washed several times with water
  7. dry with materialwith brine, dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum
  10. customThe crude material was purified by preparative layer chromatography on a 0.05×20×20 cm silica gel GF plate (Analtech, Newark, Del.)
  11. washThe low Rf band was eluted with 5% MeOH in CH2Cl2
  12. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-4a9ee2c58c014b4fa6ac19a94f60c52a
Source dataset
uspto-grants-2008_10
Patent number
US07432284B2

Reaction notes

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