Acetic Acid → HCID 13754447, compound

HRID 2118835Notes

Reaction equation

HRID 2118835 reaction equation
[CH:1](NC(C)C)([CH3:3])[CH3:2].C([Li])CCC.[C:13]([O:17][C:18]([NH:20][CH2:21][C:22]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:23])=[O:19])([CH3:16])([CH3:15])[CH3:14].[C:32]([OH:35])(=O)[CH3:33]>O1CCCC1.O>[C:13]([O:17][C:18]([NH:20][CH:21]([C:32]1([OH:35])[CH2:33][CH2:3][CH2:1][CH2:2]1)[C:22]([O:24][CH2:25][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)=[O:23])=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 7912DiisopropylamineHCID 357720Benzyl N-(tert-butoxycarbonyl)glycinateHCID 178418339Butyllithium

Product 1

HCID 13754447HCID 13754447, compoundYield 48.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

A solution of diisopropylamine (3.77 ml, 23 mmole) in 40 ml of dry tetrahydrofuran under argon was chilled to -40° C. and treated with 13 ml of a 1.71 N n-butyllithium solution (21.5 mmoles). After stirring for 20 minutes, the mixture was cooled to -78° C. and treated with a solution of N-(t-butoxycarbonyl)glycine, benzyl ester (2.65 g, 10 mmole) in 10 ml of tetrahydrofuran. The mixture became darker yellow, but remained clear. After 0.5 hours at -78° C., 0.88 ml (11.5 mmoles) of dried (4Å sieves) cyclopentanone was added and then after 15 minutes at -78° C., the mixture was warmed over 0.5 hours to -20° C., whereupon the solution darkened to a deep purple. The temperature was raised to 0° C. for 20 minutes, then 1.32 g (22 mmole) of acetic acid in 5 ml of tetrahydrofuran was added, whereupon the color was discharged, leaving a gelatinous precipitate. The mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried (sodium sulfate) and evaporated to an oil which was chromatographed on 900 ml of LPS-1 in hexane:ethyl acetate, 3:1. Evaporation of product fractions and crystallization from hexane gave, in two crops, 1.68 g of product, melting point 68°-70° C. (Rf=0.77, silica, hexane:ethyl acetate, 3:1).

Workup

  1. waitAfter 0.5 hours at -78° C.
  2. dry with material0.88 ml (11.5 mmoles) of dried (4Å sieves) cyclopentanone
  3. additionwas added
  4. waitafter 15 minutes at -78° C.
  5. temperaturethe mixture was warmed over 0.5 hours to -20° C., whereupon the solution
  6. temperatureThe temperature was raised to 0° C. for 20 minutes
  7. customleaving a gelatinous precipitate
  8. extractionextracted with ethyl acetate
  9. washThe organic layer was washed with brine
  10. dry with materialdried (sodium sulfate)
  11. customevaporated to an oil which
  12. customwas chromatographed on 900 ml of LPS-1 in hexane
  13. customEvaporation of product fractions and crystallization from hexane

Sources & evidence

ORD record
ord-c3a2c9a3e6564f679e1d3a75dccb01e3
Source dataset
uspto-grants-1987_07
Patent number
US04680388

Reaction notes

Loading…