Diisopropylamine → Methyl 2-acetyl-7-benzyloxy-8-n-propylchroman-2-carboxylate

HRID 1285263Notes

Reaction equation

HRID 1285263 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH2:13]([O:20][C:21]1[C:30]([CH2:31][CH2:32][CH3:33])=[C:29]2[C:24]([CH2:25][CH2:26][CH:27]([C:34]([O:36][CH3:37])=[O:35])[O:28]2)=[CH:23][CH:22]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[C:38](C1NC=CN=1)(=[O:40])[CH3:39].S([O-])(O)(=O)=O.[K+]>O1CCCC1>[C:38]([C:27]1([C:34]([O:36][CH3:37])=[O:35])[CH2:26][CH2:25][C:24]2[C:29](=[C:30]([CH2:31][CH2:32][CH3:33])[C:21]([O:20][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[CH:22][CH:23]=2)[O:28]1)(=[O:40])[CH3:39]

Participants

7

Reactant 5

HCID 7912DiisopropylamineHCID 516920Potassium bisulfateHCID 5389722-AcetylimidazoleHCID 14882998Methyl 7-benzyloxy-8-n-propylchroman-2-carboxylateHCID 178418339Butyllithium

Product 1

HCID 20250461Methyl 2-acetyl-7-benzyloxy-8-n-propylchroman-2-carboxylateYield 63.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-20 °C

Procedure

A 100 ml 3 neck roundbottom flask was fitted with a magnetic stirring bar, dropping funnel, serum cap, and gas inlet tube, flushed with argon and flame dried. 1.11 g or 1.54 ml (11 mmole) of diisopropylamine and 30 ml dry tetrahydrofuran were added. After cooling to -20° C., 6.43 ml of 1.71M n-butyl lithium (11 mmole) was added dropwise via syringe. The solution was stirred 15 minutes at -10° C. and then cooled to -70° C. 3.40 g (10 mmole) of the product of Example 22 in 20 ml tetrahydrofuran at -70° C. was added dropwise over a period of half hour. After stirring one additional hour at -70° C., 1.27 g (11.5 mmole) of acetylimidazole in 10 ml tetrahydrofuran was added and the reaction mixture allowed to warm slowly to -10° C. 0.5M potassium hydrogen sulfate solution was added until the pH reached 2.0, the layers were separated and 100 ml ethyl acetate was added. The organic layer was washed with 0.5M potassium hydrogen carbonate, twice with water and then dried with anhydrous magnesium sulfate. After filtration, the ethyl acetate was removed by rotary evaporation and the residual oil purified by high pressure liquid chromatography (10% ethyl acetate-hexane) to give 2.42 g (63%) of the title compound as an oil. Calc: C, 72.22; H, 6.85; Found: C, 72.43; H, 6.86.

Workup

  1. customserum cap
  2. customgas inlet tube, flushed with argon
  3. temperatureflame
  4. customdried
  5. temperaturecooled to -70° C
  6. stirringAfter stirring one additional hour at -70° C.
  7. temperatureto warm slowly to -10° C
  8. customthe layers were separated
  9. addition100 ml ethyl acetate was added
  10. washThe organic layer was washed with 0.5M potassium hydrogen carbonate, twice with water
  11. dry with materialdried with anhydrous magnesium sulfate
  12. filtrationAfter filtration
  13. customthe ethyl acetate was removed by rotary evaporation
  14. customthe residual oil purified by high pressure liquid chromatography (10% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-fbc3d81d9bfc498aa6fbd33702195f7f
Source dataset
uspto-grants-1986_01
Patent number
US04565882

Reaction notes

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