Acetaldehyde → HCID 68772154, compound

HRID 1471369Notes

Reaction equation

HRID 1471369 reaction equation
C(N[CH:5]([CH3:7])[CH3:6])(C)C.C([Li])CCC.[CH3:13][C@@H:14]1[CH2:23][CH2:22][CH2:21][C:16]2([CH2:20][CH2:19][CH2:18][CH2:17]2)[C@@H:15]1[C:24](=[O:26])C.C(=O)C.Cl.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>O1CCCC1>[CH3:13][C@@H:14]1[CH2:23][CH2:22][CH2:21][C:16]2([CH2:20][CH2:19][CH2:18][CH2:17]2)[C@@H:15]1[C:24](=[O:26])/[CH:7]=[CH:5]/[CH3:6]

Participants

9

Reactant 7

HCID 177AcetaldehydeHCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 68771601HCID 68771601, compoundHCID 178418339Butyllithium

Product 1

HCID 68772154HCID 68772154, compoundYield 33%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-30 °C

Procedure

At −60° C., a solution of diisopropylamine (4.1 ml, 28.8 mmol) in tetrahydrofuran (30 ml) was treated with n-butyl lithium (18 ml, 1.6M in hexane, 28.8 mmol). The resulting solution was stirred at −30° C. for 20 min., cooled to −70° C., and treated with a solution of crude 1-(rel-(6R,7R)-7-methylspiro[4.5]decan-6-yl)ethanone (4.3 g, 22 mmol) in tetrahydrofuran (10 ml). The resulting solution was stirred 45 min. at −70° C., and treated within 15 min. with a solution of acetaldehyde (5 ml, 88.5 mmol) in tetrahydrofuran (10 ml). After 2 h stirring, the reaction mixture was poured into 2N aqueous HCl and ice (150 ml) and extracted twice with MTBE (100 ml). The combined organic phases were washed with water (50 ml), with a saturated aqueous NaCl solution (100 ml), dried (MgSO4), and concentrated. The crude product (5.5 g) was dissolved in toluene (60 ml). The resulting solution was treated with para-toluene sulfonic acid monohydrate (0.5 g, 2.8 mmol) and heated at 60° C. for 1.5 h. The reaction mixture was cooled, poured into a cold saturated aqueous solution of NaHCO3 (100 ml) and the aqueous phase was extracted with MTBE (80 ml). The combined organic phases were washed with a saturated aqueous NaCl solution (80 ml), dried (MgSO4) and concentrated. FC (SiO2, hexane/MTBE 30:1) of the crude product (5.5 g) gave (E)-1-(rel-(6R,7R)-7-methylspiro[4.5]decan-6-yl)but-2-en-1-one (1.6 g, 33%). Boiling point: 100° C. (0.07 mbar).

Workup

  1. temperaturecooled to −70° C.
  2. stirringThe resulting solution was stirred 45 min. at −70° C.
  3. stirringAfter 2 h stirring
  4. extractionextracted twice with MTBE (100 ml)
  5. washThe combined organic phases were washed with water (50 ml), with a saturated aqueous NaCl solution (100 ml)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. dissolutionThe crude product (5.5 g) was dissolved in toluene (60 ml)
  9. temperatureheated at 60° C. for 1.5 h
  10. temperatureThe reaction mixture was cooled
  11. extractionthe aqueous phase was extracted with MTBE (80 ml)
  12. washThe combined organic phases were washed with a saturated aqueous NaCl solution (80 ml)
  13. dry with materialdried (MgSO4)
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-3940181f0e7b4e77ac92d200d415cf2d
Source dataset
uspto-grants-2015_04
Patent number
US09012391B2

Reaction notes

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