Pyridine → (4R,5R)-3-Acetylamino-4,5-dimethyl-(Z)-oct-2-enoic Acid Ethyl Ester

HRID 132668Notes

Reaction equation

HRID 132668 reaction equation
[CH2:1]([O:3][C:4](=[O:15])/[CH:5]=[C:6](\[NH2:14])/[C@H:7]([CH3:13])[C@H:8]([CH3:12])[CH2:9][CH2:10][CH3:11])[CH3:2].[C:16](Cl)(=[O:18])[CH3:17].N1C=CC=CC=1>C(Cl)Cl>[CH2:1]([O:3][C:4](=[O:15])/[CH:5]=[C:6](\[NH:14][C:16](=[O:18])[CH3:17])/[C@H:7]([CH3:13])[C@H:8]([CH3:12])[CH2:9][CH2:10][CH3:11])[CH3:2]

Participants

5

Reactant 3

HCID 1049PyridineHCID 6367Acetyl chlorideHCID 86597974(4R,5R)-3-Amino-4,5-dimethyl-(Z)-oct-2-enoic Acid Ethyl Ester

Product 1

HCID 25232468(4R,5R)-3-Acetylamino-4,5-dimethyl-(Z)-oct-2-enoic Acid Ethyl EsterYield 93.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-20 °C

Procedure

To a 1 L 3-necked round bottom flask equipped with an overhead stirrer, thermocouple, addition funnel, and nitrogen inlet, was charged 150 g (0.70 mol) of (4R,5R)-3-amino-4,5-dimethyl-(Z)-oct-2-enoic acid ethyl ester and 50 mL of dry CH2Cl2. The reaction mixture was cooled to −20° C. To the mixture was added, successively, acetyl chloride (60 mL, 0.84 mol) and pyridine (66.8 g, 0.84 mol) over 0.5-hour time intervals. After the additions, the mixture was stirred at −20° C. to 0° C. for 2 hours and then filtered to remove the pyridine.HCl salt. The filtrate was diluted with 200 mL of CH2Cl2 and washed 2× with aliquots of aq NH4Cl. The organic solution was treated with silica gel (50 g), MgSO4 (20 g) and charcoal (20 g), and stirred at room temperature for 0.5 hours. The solids were filtered off and the filtrate was concentrated under reduced pressure to give 166.5 g (93% yield) of the titled compound as an oil: 1H NMR (400 MHz, CHLOROFORM-D) 0.85 (t, J=7.4 Hz, 3H), 0.95 (d, J=6.8 Hz, 3H), 1.00 (d, J=7.0 Hz, 3H), 1.11 (m, 1H) 1.29 (t, J=5.8 Hz, 3H), 1.40-1.25 (m, 2H), 1.65 (m, 1H) 2.13 (s, 3H), 3.80 (m, 1H) 4.2-4.14 (m, 3H), 5.01 (s, 1H), 11.28 (s, 1H).

Workup

  1. customTo a 1 L 3-necked round bottom flask equipped with an overhead stirrer
  2. additionthermocouple, addition funnel, and nitrogen inlet
  3. additionTo the mixture was added
  4. filtrationfiltered
  5. customto remove the pyridine
  6. additionThe filtrate was diluted with 200 mL of CH2Cl2
  7. washwashed 2× with aliquots of aq NH4Cl
  8. additionThe organic solution was treated with silica gel (50 g), MgSO4 (20 g) and charcoal (20 g)
  9. stirringstirred at room temperature for 0.5 hours
  10. filtrationThe solids were filtered off
  11. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-64d14dd1af1d4f3191ec19ab7a303163
Source dataset
uspto-grants-2008_06
Patent number
US07388023B2

Reaction notes

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