Dimethylformamide → HCID 13732926, compound

HRID 1731819Notes

Reaction equation

HRID 1731819 reaction equation
[H-].[Na+].F[C:4]1[CH:18]=[CH:17][CH:16]=[CH:15][C:5]=1[CH2:6][C:7]1([OH:14])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1.CN(C)C=O>C1C=CC=CC=1>[C:7]12([CH2:6][C:5]3[CH:15]=[CH:16][CH:17]=[CH:18][C:4]=3[O:14]1)[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]2

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 137329251-[(2-Fluorophenyl)methyl]cycloheptan-1-ol

Product 1

HCID 13732926HCID 13732926, compoundYield 44.2%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent2×

Procedure

To a stirred suspension of 23.32 g of sodium hydride (as a 50% dispersion in mineral oil) in 1.5 liters of benzene (dried over molecular sieves) was rapidly added a solution of 69.9 g of 1-(2-fluorobenzyl)-1-hydroxycycloheptane in 500 ml of benzene. After the addition the mixture was heated to reflux under nitrogen, and 100 ml of dimethylformamide (distilled over BaO) was added to the refluxing mixture. After 118 hours of reflux, the mixture was cooled in ice water and treated with 2.0 liters distilled water. After stirring for a few minutes the phases were separated and the aqueous phase was extracted with hexane (once with 2 liters and twice with one liter). The combined organic extracts were washed with water (1.0 liter) and saturated sodium chloride solution (1.0 liter) and thereafter dried over anhydrous sodium sulfate. Filtration and concentration in vacuo afforded 65.9 g of a crude oil which was given a preliminary purification by preparative HPLC using dichloromethane as solvent. This treatment afforded 28.09 g of product as well as 9.2 g of unreacted starting material. The product was further purified by preparatory HPLC, using hexane/dichloromethane (4:1) as a solvent. This treatment afforded 21.18 g of product as an oil which was 97.6% pure by GC. Vacuum distillation of this material afforded 6.17 g of pure distillate, b.p. 85°-87° C. @ 0.20 mm.

Workup

  1. additionAfter the addition the mixture
  2. temperaturewas heated
  3. temperatureto reflux under nitrogen
  4. temperatureAfter 118 hours of reflux
  5. additiontreated with 2.0 liters
  6. distillationdistilled water
  7. customwere separated
  8. extractionthe aqueous phase was extracted with hexane (once with 2 liters
  9. washThe combined organic extracts were washed with water (1.0 liter) and saturated sodium chloride solution (1.0 liter)
  10. dry with materialdried over anhydrous sodium sulfate
  11. filtrationFiltration and concentration in vacuo
  12. customafforded 65.9 g of a crude oil which
  13. customa preliminary purification by preparative HPLC

Sources & evidence

ORD record
ord-758033cc13614b61b3dd4ca1dd8ee661
Source dataset
uspto-grants-1986_11
Patent number
US04623657

Reaction notes

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