Acetic Acid → HCID 129281815, compound

HRID 2118839Notes

Reaction equation

HRID 2118839 reaction equation
C(NC(C)C)(C)C.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]1(=[O:36])[CH2:35][CH2:34][CH2:33]1.C(O)(=O)C>O1CCCC1.O.CCCCCC>[C:13]([O:17][C:18]([NH:20][CH:21]([C:32]1([OH:36])[CH2:35][CH2:34][CH2:33]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

9

Reactant 5

HCID 176Acetic AcidHCID 7912DiisopropylamineHCID 14496CyclobutanoneHCID 357720Benzyl N-(tert-butoxycarbonyl)glycinateHCID 178418339Butyllithium

Product 1

HCID 129281815HCID 129281815, compoundYield 77.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent4×HCID 8058HexaneSolvent

Conditions

Temperature
-40 °C

Procedure

A solution of diisopropylamine (9.7 ml, 70 mmoles) in 150 ml of dry tetrahydrofuran at -40° C. under argon was treated with 39 ml (64.5 mmoles) of 1.71N n-butyllithium is hexane and the pale yellow solution stirred at -40° C. for 20 minutes. The solution was cooled to -78° C., and a solution of 7.95 g (30 mmoles) of N-(t-butoxycarbonyl)glycine, benzyl ester in 30 ml of dry tetrahydrofuran was dripped in over 5 minutes, resulting in a dark yellow solution, and, after 20 minutes, a slight turbidity. After 0.5 hours, a solution of 2.42 g (2.0 ml, 34.5 mmoles) of cyclobutanone in 30 ml of tetrahydrofuran was added. The resulting yellow turbid mixture was stirred at -78° C. for 15 minutes, then placed in a 0° C. ice bath for 2 hours. At an internal temperature of -25° C. (1 hour), the solution became clear, and at -15° C. turned dark purple. It was stirred at 0° C. for 0.5 hours, then treated with 3.96 g (66 mmoles) of glacial acetic acid in 15 ml of tetrahydrofuran, giving a turbid, light yellow mixture. This was poured into 500 ml of cold water and extracted twice with ethyl acetate. The extracts were washed with 2% potassium bisulfate, 5% sodium bicarbonate, and brine, dried (sodium sulfate) and evaporated to a thick oil. Chromatography on 800 ml of LPS-1 in hexane:ethyl acetate (2:1) and combination of the product fractions (Rf=0.29) gave 7.8 g of product as an oil.

Workup

  1. temperatureThe solution was cooled to -78° C.
  2. customwas dripped in over 5 minutes
  3. customresulting in a dark yellow solution
  4. waitafter 20 minutes
  5. waitAfter 0.5 hours
  6. stirringwas stirred at -78° C. for 15 minutes
  7. customplaced in a 0° C.
  8. customfor 2 hours
  9. customAt an internal temperature of -25° C. (1 hour)
  10. customat -15° C.
  11. stirringIt was stirred at 0° C. for 0.5 hours
  12. customgiving a turbid, light yellow mixture
  13. extractionextracted twice with ethyl acetate
  14. washThe extracts were washed with 2% potassium bisulfate, 5% sodium bicarbonate, and brine
  15. dry with materialdried (sodium sulfate)
  16. customevaporated to a thick oil

Sources & evidence

ORD record
ord-c37fc6d61ec94f2caa7a5e677e9b7fa7
Source dataset
uspto-grants-1987_07
Patent number
US04680388

Reaction notes

Loading…