Pyridine → HCID 12017802, compound

HRID 990326Notes

Reaction equation

HRID 990326 reaction equation
[CH2:1]([O:8][C:9](=[O:16])[C@H:10]([NH2:15])[CH2:11][CH:12]([CH3:14])[CH3:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[C:23](Cl)(Cl)=[O:24].[CH2:27](Cl)Cl>C1(C)C=CC=CC=1.C(Cl)(Cl)Cl>[CH2:1]([O:8][C:9](=[O:16])[C@H:10]([NH:15][C:23]([N:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:27]1)=[O:24])[CH2:11][CH:12]([CH3:13])[CH3:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 6344DichloromethaneHCID 6371PhosgeneHCID 6942172HCID 6942172, compound

Product 1

HCID 12017802HCID 12017802, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6212ChloroformSolvent

Conditions

Temperature
0 °C

Procedure

A solution of (R)-2-amino-4-methyl-pentanoic acid benzyl ester (14.1 g, 63.6 mmol) and pyridine (25 mL, 0.31 mmol) in 400 mL of CH2Cl2 was cooled to 0° C. and treated rapidly with phosgene (40 mL of a 1.9 M solution in toluene) in one portion. The resulting solution was stirred at 0° C. for 2 hours and then treated with hexamethyleneimine (9.3 mL, 82.7 mmol) in CHCl3 (25 mL). The resulting solution was warmed to room temperature and concentrated. The residue was dissolved in ether and washed with aqueous 1N HCl solution. The organic phase was dried (MgSO4), filtered and concentrated. The crude residue was purified by chromatography (silica gel, 2:1 heptane/ethyl acetate) to give the title compound as a yellow solid (4.96 g, 68%); mp 88-89° C. APCI-MS m/z 347 (MH+).

Workup

  1. temperatureThe resulting solution was warmed to room temperature
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in ether
  4. washwashed with aqueous 1N HCl solution
  5. dry with materialThe organic phase was dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude residue was purified by chromatography (silica gel, 2:1 heptane/ethyl acetate)

Sources & evidence

ORD record
ord-bff0a47ac2ac477ea87b7aaa9e1d8cf2
Source dataset
uspto-grants-2002_10
Patent number
US06458781B1

Reaction notes

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