Triethylamine → N-(2,2-Dimethylcyclopropanecarbonyl)-DL-norleucine t-butyl ester

HRID 2290388Notes

Reaction equation

HRID 2290388 reaction equation
[C:1]([O:5][C:6](=[O:13])[CH:7]([CH2:9][CH2:10][CH2:11][CH3:12])[NH2:8])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:21][C:22]1([CH3:28])[CH2:24][CH:23]1[C:25](Cl)=[O:26]>C(Cl)Cl>[C:1]([O:5][C:6](=[O:13])[CH:7]([CH2:9][CH2:10][CH2:11][CH3:12])[NH:8][C:25]([CH:23]1[CH2:24][C:22]1([CH3:28])[CH3:21])=[O:26])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 110079512,2-Dimethylcyclopropanecarbonyl chlorideHCID 12451445Tert-butyl 2-aminohexanoate

Product 1

HCID 15595771N-(2,2-Dimethylcyclopropanecarbonyl)-DL-norleucine t-butyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 8.98 g (48 mmole) of DL-norleucine t-butyl ester and 5.05 g (50 mmole) of triethylamine in 100 ml of CH2Cl2 stirred in an ice bath under a drying tube was added dropwise (over a period of 75 min.) a solution of 6.39 g (48 mmole) of 2,2-dimethylcyclopropanecarbonyl chloride (M. Elliot and N. R. James, British Pat. No. 1,260,847 (1972)) in 50 ml of CH2Cl2. Precipitation of Et3N HCl occurred during the addition, especially toward the end. As the ice gradually melted, the mixture was allowed to warm to room temperature. After 16 hrs, the mixture was shaken with 200 ml of 0.5 N HCl. The CH2Cl2 fraction was washed with an additional 200 ml of 0.5 N HCl, then with 2×200 ml of 0.5 N NaOH, and finally 200 ml of H2O. The CH2Cl2 fraction was dried with MgSO4, treated with charcoal, and filtered through Celite. The filtrate was concentrated on the rotovac (finally under high vacuum). Yield of light orange residual oil=11.93 g (88%). Tlc (2:1 hexane-EtOAc) showed a single spot. NMR and IR were in accord with the assigned structure. After standing for several days, the unused porition of this material crystallized: m.p. 52->65°.

Workup

  1. customPrecipitation of Et3N HCl
  2. additionoccurred during the addition, especially toward the end
  3. washThe CH2Cl2 fraction was washed with an additional 200 ml of 0.5 N HCl
  4. dry with materialThe CH2Cl2 fraction was dried with MgSO4
  5. additiontreated with charcoal
  6. filtrationfiltered through Celite
  7. concentrationThe filtrate was concentrated on the rotovac (finally under high vacuum)
  8. waitAfter standing for several days
  9. customthe unused porition of this material crystallized

Sources & evidence

ORD record
ord-fd807a6770e04c659c8addea0f836757
Source dataset
uspto-grants-1986_10
Patent number
US04616038

Reaction notes

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