Sodium t-butoxide → 5-[4-(2-Azepan-1-yl-ethoxy)-phenyl]-9-fluoro-5H-6-oxa-chrysen-2-ol

HRID 1513964Notes

Reaction equation

HRID 1513964 reaction equation
[N:1]1([CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]([OH:37])[C:18]3[C:27]([C:28]4[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=4F)=[CH:26][CH:25]=[C:24]4[C:19]=3[CH:20]=[CH:21][C:22]([OH:36])=[CH:23]4)=[CH:13][CH:12]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CC(C)([O-])C.[Na+]>CN(C=O)C.O>[N:1]1([CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]3[O:37][C:29]4[C:28](=[CH:33][C:32]([F:34])=[CH:31][CH:30]=4)[C:27]4[C:18]3=[C:19]3[C:24](=[CH:25][CH:26]=4)[CH:23]=[C:22]([OH:36])[CH:21]=[CH:20]3)=[CH:13][CH:12]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 23676156Sodium t-butoxideHCID 670045865-{[4-(2-Azepan-1-yl-ethoxy)-phenyl]-hydroxymethyl}-6-(2,5-difluorophenyl)-naphthalen-2-ol

Product 1

HCID 575525185-[4-(2-Azepan-1-yl-ethoxy)-phenyl]-9-fluoro-5H-6-oxa-chrysen-2-ol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

Dissolve 5-{[4-(2-azepan-1-yl-ethoxy)-phenyl]-hydroxymethyl}-6-(2,5-difluorophenyl)-naphthalen-2-ol (770 mg, 1.54 mmol) in 20 mL dry DMF and add sodium t-butoxide (1.18 g, 12.32 mmol). Heat the mixture to 50° C. for two hours. Dilute with water and extract multiple times with methylene chloride. Dry the organic layer and purify on a silica gel column eluting with a 0-10% methanol/methylene chloride gradient. The yield is 370 mg (50%): 1H-NMR (CDCl3, 300 MHz) δ7.76 (dd, J=12.6, 8.4 Hz, 2H); 7.58 (d, J=9.0 Hz, 1H); 7.43-7.40 (m, 1H); 7.15 (d, J=2.4 Hz, 1H); 7.05-7.01 (m, 3H); 6.89 (s, 1H); 6.83-6.80 (m, 2H); 6.66-6.63 (m, 2H); 4.00-3.98 (m, 2H); 2.92-2.92 (m, 2H); 2.78-2.78 (m, 4H); 1.66-1.59 (m, 8H). The racemic compound is purified using chiral chromatography (conditions P). The two isomers eluted with retention times of 9.9 and 13.5 minutes.

Workup

  1. extractionextract multiple times with methylene chloride
  2. customDry the organic layer
  3. custompurify on a silica gel column
  4. washeluting with a 0-10% methanol/methylene chloride gradient
  5. customThe racemic compound is purified
  6. washThe two isomers eluted with retention times of 9.9 and 13.5 minutes

Sources & evidence

ORD record
ord-b6933370dfe44e7fbaf6f0af0261ba80
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

Loading…