Sodium Bicarbonate → 5-[4-(2-Azepan-1-yl-ethoxy)-phenyl]-10-fluoro-5H-6-oxa-chrysen-2-ol

HRID 1513967Notes

Reaction equation

HRID 1513967 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[C:35]([F:36])=[CH:34][CH:33]=[CH:32][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+].C(=O)(O)[O-].[Na+].C(Cl)(Cl)Cl.C(O)(C)C>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:31]4[C:30](=[C:35]([F:36])[CH:34]=[CH:33][CH:32]=4)[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

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 21906603Chloroform isopropyl alcoholHCID 23664628LithiumtriethylborohydrideHCID 67004735[4-(2-Azepan-1-yl-ethoxy)-phenyl]-[2-(2,6-difluoro-phenyl)-6-hydroxy-naphthalen-1-yl]-methanone

Product 1

HCID 114658405-[4-(2-Azepan-1-yl-ethoxy)-phenyl]-10-fluoro-5H-6-oxa-chrysen-2-olYield 68%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

Dissolve [4-(2-azepan-1-yl-ethoxy)-phenyl]-[2-(2,6-difluoro-phenyl)-6-hydroxy-naphthalen-1-yl]-methanone (1.3 g, 2.6 mmol) in 125 mL dioxane and add 20 mL (20 mmol) of a 1.0 M solution of lithium triethylborohydride in THF. Stir at room temperature for one hour, then heat at 100° C. for three hours. Pour the reaction into a two phase system consisting of saturated sodium bicarbonate and an organic phase of a 3/1 mixture of chloroform/isopropanol. Extract in a reparatory funnel, separate the organic layer and dry over 3 Å molecular sieves. Evaporate to give 1.5 g of slightly impure product. Purify on a silica column eluting with 0-10% methanol/methylene chloride gradient to give 850 mg (68%) of racemic product: 1H-NMR (CDCl3, 400 MHz) δ8.18 (d, J=8.4 Hz, 1H); 7.73 (d, J=8.8 Hz, 1H); 7.52 (d, J=9.2 Hz, 1H); 7.21 (d, J=2.4 Hz, 1H); 7.08-6.99 (m, 5H); 6.88 (s, 1H); 6.72-6.61 (m, 4H); 4.24-4.23 (m, 2H); 3.26-3.26 (m, 6H); 1.87-1.87 (m, 4H); 1.66-1.66 (m, 4H). The racemic mixture is purified using chiral chromatography (conditions F). The two isomers eluted with retention times of 7.9 and 9.0 minutes.

Workup

  1. temperatureheat at 100° C. for three hours
  2. additionPour
  3. customthe reaction into a two phase system
  4. extractionExtract in a reparatory funnel
  5. customseparate the organic layer
  6. customdry over 3 Å molecular sieves
  7. customEvaporate
  8. customto give 1.5 g of slightly impure product
  9. customPurify on a silica column
  10. washeluting with 0-10% methanol/methylene chloride gradient

Sources & evidence

ORD record
ord-9e0c9a9adae34770a2dbbc20caf793a7
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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