Hydrochloric Acid → HCID 13912366, compound

HRID 2119098Notes

Reaction equation

HRID 2119098 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[C:13]([O:16][CH2:17][CH3:18])(=[O:15])[CH3:14].[C:19]([NH:26][C@H:27]([CH:35]=[O:36])[CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20].Cl>O1CCCC1.CCCCCCC>[C:22]([O:21][C:19]([NH:26][C@@H:27]([CH2:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)[CH:35]([OH:36])[CH2:14][C:13]([O:16][CH2:17][CH3:18])=[O:15])=[O:20])([CH3:25])([CH3:23])[CH3:24]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 8857Ethyl AcetateHCID 6998013tert-butyl N-[(2S)-1-oxo-3-phenylpropan-2-yl]carbamateHCID 178418339Butyllithium

Product 1

HCID 13912366HCID 13912366, compoundYield 90.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8900HeptaneSolvent

Procedure

A solution of 92.4 ml (0.706 moles) of diisopropylamine in 600 ml of tetrahydrofuran was cooled to -35° and 271.1 ml (0.706 moles) of a 2.6M solution of n-butyl lithium in heptane was added slowly. The solution was then cooled to -85° in an ethanol/liquid nitrogen bath and 68.9 g (0.706 moles) of ethyl acetate was added slowly keeping the reaction temperature below -80°. After stirring for 15 minutes, a solution of 125.5 g (0.504 moles) of Boc-phenylalaninal [J. A. Fehrentz and B. Castro, Synthesis, 676 (1983).] in 1 L. of tetrahydrofuran, precooled to -78°, was added dropwise, keeping the temperature below -80°. After stirring at -80° for 15 minutes, the solution was allowed to warm to -5° and 400 ml of 12% hydrochloric acid was added. The pH was adjusted to 2.0 and the solution extracted twice with ether. The combined ether solution was washed with 1N hydrochloric acid, water, saturated sodium bicarbonate, and then with saturated sodium chloride solution. After drying over magnesium sulfate the ether was removed under reduced pressure to give 154 g. (90.6% yield) of the crude product as a white solid sufficiently pure for use in the next step.

Workup

  1. temperatureThe solution was then cooled to -85° in an ethanol/liquid nitrogen bath
  2. customthe reaction temperature below -80°
  3. customCastro, Synthesis, 676 (1983)
  4. customprecooled to -78°
  5. additionwas added dropwise
  6. customthe temperature below -80°
  7. stirringAfter stirring at -80° for 15 minutes
  8. temperatureto warm to -5°
  9. extractionthe solution extracted twice with ether
  10. washThe combined ether solution was washed with 1N hydrochloric acid, water, saturated sodium bicarbonate
  11. dry with materialAfter drying over magnesium sulfate the ether
  12. customwas removed under reduced pressure
  13. customto give 154 g

Sources & evidence

ORD record
ord-d447e053f67d46d8a185ad39f4d315a1
Source dataset
uspto-grants-1987_07
Patent number
US04681972

Reaction notes

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