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

HRID 1719178Notes

Reaction equation

HRID 1719178 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-b0049f0b62fd4bc78e2e1342d1b2fd36
Source dataset
uspto-grants-1985_09
Patent number
US04539208

Reaction notes

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