Acetic Acid → HCID 131719064, compound

HRID 1450178Notes

Reaction equation

HRID 1450178 reaction equation
[NH:1]([C:20]([O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:21])[C@@H:2]([C:10]([N:12]1[CH2:19][CH2:18][CH2:17][C@H:13]1[C:14]([OH:16])=[O:15])=[O:11])[CH2:3][CH:4]1[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]1.CI.[C:32](O)(=O)C.[OH-].[Na+]>O1CCCC1.C1OCCOCCOCCOCCOCCOC1.O>[N:1]([C:20]([O:22][CH2:23][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)=[O:21])([CH3:32])[C@@H:2]([C:10]([N:12]1[CH2:19][CH2:18][CH2:17][C@H:13]1[C:14]([OH:16])=[O:15])=[O:11])[CH2:3][CH:4]1[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9]1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 6328Methyl iodideHCID 14798Sodium HydroxideHCID 131719065HCID 131719065, compound

Product 1

HCID 131719064HCID 131719064, compoundYield 90%

Reagents, catalysts & solvents 3

HCID 2855718-Crown-6CatalystHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of KH (19.3 g, 25% suspension in oil, mmol) in tetrahydrofuran (100 mL) at 0° C. was slowly added (over 25 min) a solution of Cbz-D-Cha-Pro-OH (16.8 g, 41.7 mmol) in tetrahydrofuran (50 mL). During this addition period the internal temperature was monitored and maintained at less than 10° C. To this solution was then slowly added a solution of methyl iodide (5 mL, 80 mmol) and 18-crown-6 (661 mg, 2.5 mmol), again maintaining the internal temperature below 10° C. After 2 h acetic acid (10 mL) was added dropwise, followed by water (10 mL). The solution was then poured into cold water and the pH was adjusted to 9 with 2N NaOH. The aqueous base was washed twice with diethyl ether and then acidified to pH 2 with conc. HCl and extracted four times with chloroform. The chloroform extracts were combined, dried over Na2SO4, filtered and concentrated in vacuo to afford 15.7 g (90%) of a pale yellow solid.

Workup

  1. additionDuring this addition period the internal temperature
  2. temperaturemaintained at less than 10° C
  3. temperatureagain maintaining the internal temperature below 10° C
  4. washThe aqueous base was washed twice with diethyl ether
  5. extractionextracted four times with chloroform
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3aac0b9051304e109ffe2d443abbdcd6
Source dataset
uspto-grants-1997_02
Patent number
US05602101

Reaction notes

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