1,4-Dioxane → HCID 67004818, compound

HRID 1513958Notes

Reaction equation

HRID 1513958 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([C:12]([C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][N:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)=[CH:16][CH:15]=1)=[O:13])=[C:7]([C:29]1[CH:34]=[CH:33][C:32]([F:35])=[C:31]([F:36])[C:30]=1F)[CH:6]=[CH:5]2.O1CCOCC1.C([BH-](CC)CC)C.[Li+].C(=O)(O)[O-].[Na+].C(Cl)(Cl)[Cl:58].C(O)(C)C>>[ClH:58].[F:36][C:31]1[C:32]([F:35])=[CH:33][CH:34]=[C:29]2[C:30]=1[O:13][CH:12]([C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][N:23]3[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]3)=[CH:16][CH:15]=1)[C:8]1[C:7]2=[CH:6][CH:5]=[C:4]2[C:9]=1[CH:10]=[CH:11][C:2]([OH:1])=[CH:3]2

Participants

6

Reactant 5

HCID 312751,4-DioxaneHCID 516892Sodium BicarbonateHCID 21906603Chloroform isopropyl alcoholHCID 23664628LithiumtriethylborohydrideHCID 67004288HCID 67004288, compound

Product 1

HCID 67004818HCID 67004818, compound

Conditions

Temperature
90 °C

Procedure

Charge a flask with [6-hydroxy-2-(2,3,4-trifluoro-phenyl)-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone (620 mg, 1.23 mmol) and add 250 mL dioxane. Start stirring and add to this 20 mL of a 1.0 M solution of lithium triethylborohydride in UV at room temperature. Stopper flask and stir for one hour. Heat the flask to 90° C. under nitrogen and follow reaction by LC/MS. Heat the reaction for a total of 18 hours. Pour the reaction into 300 mL of a mixture of 3/1 chloroform/isopropanol and 300 mL of saturated sodium bicarbonate solution. Separate the organic layer and dry over 3 Å molecular sieves. Evaporate to dryness and purify on a silica gel column eluting with 3% methanol/methylene chloride. Evaporate and convert to the hydrochloride salt using acetonitrile/water with 1N HCl and lyophilize. The yield is 295 mg (46%). 1H-NMR (CD3OD, 400 MHz) δ7.90-7.87 (m, 1H); 7.79 (d, J=8.8 Hz, 1H); 7.65 (d, J=8.8 Hz, 1H); 7.59-7.55 (m, 1H); 7.19 (d, J=2.4 Hz, 1H); 7.11-7.05 (m, 3H); 6.88-6.83 (m, 1H); 6.81-6.75 (m, 2H); 4.10-4.07 (m, 2H); 2.93-2.91 (m, 2H); 2.71-2.71 (m, 4H); 1.67-1.63 (m, 4H); 1.51-1.50 (m, 2H). The racemic compound is purified using chiral chromatography using chiral chromatography (conditions O). The two isomers eluted with retention times of 5.2 and 7.4 minutes.

Workup

  1. stirringStopper flask and stir for one hour
  2. customreaction by LC/MS
  3. temperatureHeat
  4. customthe reaction for a total of 18 hours
  5. additionPour
  6. customSeparate the organic layer
  7. customdry over 3 Å molecular sieves
  8. customEvaporate to dryness
  9. custompurify on a silica gel column
  10. washeluting with 3% methanol/methylene chloride
  11. customEvaporate
  12. customThe racemic compound is purified
  13. washThe two isomers eluted with retention times of 5.2 and 7.4 minutes

Sources & evidence

ORD record
ord-1a670e54e0104f439b2b1fb9124b5051
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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