Lithium → 5-[4-(2-Azepan-1-yl-ethoxy)-phenyl]-7,9-difluoro-5H-6-oxa-chrysen-2-ol

HRID 1513969Notes

Reaction equation

HRID 1513969 reaction equation
[N:1]1([CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([C:19]3[C:28]4[C:23](=[CH:24][C:25]([OH:29])=[CH:26][CH:27]=4)[CH:22]=[CH:21][C:20]=3[C:30]3[CH:35]=[C:34]([F:36])[CH:33]=[C:32]([F:37])[C:31]=3F)=[O:18])=[CH:13][CH:12]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C([BH-](CC)CC)C.[Li+].[Li]>O1CCOCC1.C1COCC1>[N:1]1([CH2:8][CH2:9][O:10][C:11]2[CH:12]=[CH:13][C:14]([CH:17]3[O:18][C:35]4[C:30](=[CH:31][C:32]([F:37])=[CH:33][C:34]=4[F:36])[C:20]4[C:19]3=[C:28]3[C:23](=[CH:22][CH:21]=4)[CH:24]=[C:25]([OH:29])[CH:26]=[CH:27]3)=[CH:15][CH:16]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 3028194LithiumHCID 23664628Lithiumtriethylborohydride2×HCID 67004284[4-(2-Azepan-1-yl-ethoxy)-phenyl]-[6-hydroxy-2-(2,3,5-trifluoro-phenyl)-naphthalen-1-yl]-methanone

Product 1

HCID 575525645-[4-(2-Azepan-1-yl-ethoxy)-phenyl]-7,9-difluoro-5H-6-oxa-chrysen-2-ol

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

Dissolve [4-(2-azepan-1-yl-ethoxy)-phenyl]-[6-hydroxy-2-(2,3,5-trifluoro-phenyl)-naphthalen-1-yl]-methanone (2.63 g, 5.1 mmol) in 60 mL dioxane and add 10 mL of a 1.0 M solution of lithium triethylborohydride in THF. At the end of one hour, add another 10 mL of the lithium reagent mixture is added and gently warm the reaction. After a further one hour, add an additional 25 ml of lithium triethylborohydride and heat the reaction to reflux and hold for 8 hours. Cool the reaction and quench with water. Extract the water with methylene chloride, dry the organic layer with molecular sieves and concentrate. Purify on a silica gel column eluting with a 0-10% methanol/methylene chloride gradient.

Workup

  1. additionis added
  2. temperaturegently warm
  3. customthe reaction
  4. temperatureheat
  5. customthe reaction
  6. temperatureto reflux
  7. waithold for 8 hours
  8. temperatureCool
  9. customthe reaction
  10. customquench with water
  11. extractionExtract the water with methylene chloride
  12. customdry the organic layer with molecular sieves
  13. concentrationconcentrate
  14. customPurify on a silica gel column
  15. washeluting with a 0-10% methanol/methylene chloride gradient

Sources & evidence

ORD record
ord-ebc6d72737bd48789ddab838ddd632bb
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

Loading…