Hydrochloric Acid → HCID 58991883, compound

HRID 2220579Notes

Reaction equation

HRID 2220579 reaction equation
[H-].[Na+].[O:3]1[C:7]2([CH2:12][CH2:11][CH:10]([CH:13]3[CH2:18][CH:17]([OH:19])[CH:16]([C:20]4[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH3:28])=[C:22]([F:29])[C:21]=4F)[CH2:15][CH2:14]3)[CH2:9][CH2:8]2)[O:6][CH2:5][CH2:4]1.O.Cl>CCCCC.C1(C)C=CC=CC=1.CN(C=O)C>[O:6]1[C:7]2([CH2:8][CH2:9][CH:10]([C@H:13]3[CH2:18][C@H:17]4[O:19][C:21]5[C:22]([F:29])=[C:23]([O:26][CH2:27][CH3:28])[CH:24]=[CH:25][C:20]=5[C@@H:16]4[CH2:15][CH2:14]3)[CH2:11][CH2:12]2)[O:3][CH2:4][CH2:5]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 24758Sodium hydrideHCID 58991874HCID 58991874, compound

Product 1

HCID 58991883HCID 58991883, compound

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 8003PentaneSolvent

Conditions

Temperature
90 °C

Procedure

30.0 g (0.75 mol) of sodium hydride (60% suspension in mineral oil) are washed repeatedly with n-pentane and suspended in 2500 ml of toluene. The suspension is heated to 90° C., and a solution of 101.5 g (0.26 mol) of 5-(1,4-dioxaspiro[4.5]dec-8-yl)-2-(4-ethoxy-2,3-difluorophenyl)cyclohexanol in 500 ml of DMF is metered in slowly. The batch is stirred at 90° C. for 20 h, cooled and hydrolysed using water. The mixture is neutralised by addition of 2 N hydrochloric acid, and the organic phase is separated off. The aqueous phase is extracted with toluene, and the combined organic phases are washed with sat. sodium chloride solution. The solution is dried using sodium sulfate and concentrated to dryness under reduced pressure. The crude product obtained is firstly purified by column chromatography (SiO2, toluene:ethyl acetate=8:2) and then recrystallised successively from toluene and toluene:ethanol (3:1), giving (±)-(3R*,4aR*,9bS*)-3-(1,4-dioxaspiro[4.5]dec-8-yl)-7-ethoxy-6-fluoro-1,2,3,4,4a,9b-hexahydrodibenzofuran as colourless, crystalline solid.

Workup

  1. temperaturecooled
  2. customthe organic phase is separated off
  3. extractionThe aqueous phase is extracted with toluene
  4. washthe combined organic phases are washed with sat. sodium chloride solution
  5. customThe solution is dried
  6. concentrationconcentrated to dryness under reduced pressure
  7. customThe crude product obtained
  8. customis firstly purified by column chromatography (SiO2, toluene:ethyl acetate=8:2)
  9. customrecrystallised successively from toluene and toluene:ethanol (3:1)

Sources & evidence

ORD record
ord-5011484196144c6db93605f50e0419e6
Source dataset
uspto-grants-2008_08
Patent number
US07417157B2

Reaction notes

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