2,6-Lutidine → HCID 11373114, compound

HRID 1247766Notes

Reaction equation

HRID 1247766 reaction equation
S(Cl)(Cl)=O.[N+:5]([C:8]1[CH:43]=[CH:42][C:11]([CH2:12][O:13][C:14](=[O:41])[CH:15](O)[N:16]2[CH:19]([S:20][CH2:21][C:22](=O)[CH:23]3[CH2:27][CH2:26][CH2:25][O:24]3)[CH:18]([NH:29]C(=O)CC3C=CC=CC=3)[C:17]2=[O:39])=[CH:10][CH:9]=1)([O-:7])=[O:6].N1C(C)=CC=CC=1C.CP(C)C.O1CCCC1.P(Cl)(Cl)(Cl)(Cl)Cl.N1C=CC=CC=1C>ClCCl.C(O)(C)C>[N+:5]([C:8]1[CH:43]=[CH:42][C:11]([CH2:12][O:13][C:14]([C:15]2[N:16]3[CH:19]([S:20][CH2:21][C:22]=2[CH:23]2[CH2:27][CH2:26][CH2:25][O:24]2)[CH:18]([NH2:29])[C:17]3=[O:39])=[O:41])=[CH:10][CH:9]=1)([O-:7])=[O:6]

Participants

10

Reactant 7

HCID 79372,6-LutidineHCID 79752-MethylpyridineHCID 8028TetrahydrofuranHCID 24386Thionyl ChlorideHCID 24819Phosphorus pentachlorideHCID 68983TrimethylphosphineHCID 11786242HCID 11786242, compound

Product 1

HCID 11373114HCID 11373114, compoundYield 170.3%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-40 °C

Procedure

Thionyl chloride (45 ml, 0.615 mol) was added dropwise to a solution of hydroxy-{2-oxo-4-[2-oxo-2-(tetrahydrofuran-2-yl)-ethylsulfanyl]-3-phenylacetylamino-azetidin-1-yl}-acetic acid 4-nitro-benzyl ester (202 g, 0.362 mol) and 2,6-lutidine (58 ml, 0.500 mol) in dichloromethane (4 liters) at −20° C. After stirring for 1 hour, the solution was washed twice with saturated sodium chloride (1 liter) and concentrated. To the concentrated solution was added trimethylphosphine in tetrahydrofuran solution (110 ml, 3M, 330 mmol), the solution stirred for 1 hour, washed with diluted sodium hydrogen carbonate and saturated sodium chloride. After stirring at reflux for 16 hours, the solution was washed with water and saturated sodium chloride. The solution was concentrated and cooled to −40° C. followed by a dropwise addition of phosphorus pentachloride (104 g, 0.5 mol). α-Picoline (92 ml) in dichloromethane (60 ml) solution was added while maintaining the temperature between −40° C. to 30° C. The mixture was stirred for 1 hour followed by the addition of isopropanol (660 ml). The reaction mixture was warmed to 22° C., granulated, filtered and dried to give the title compound (250 g, 45%).

Workup

  1. washthe solution was washed twice with saturated sodium chloride (1 liter)
  2. concentrationconcentrated
  3. stirringthe solution stirred for 1 hour
  4. washwashed with diluted sodium hydrogen carbonate and saturated sodium chloride
  5. stirringAfter stirring
  6. temperatureat reflux for 16 hours
  7. washthe solution was washed with water and saturated sodium chloride
  8. concentrationThe solution was concentrated
  9. temperaturewhile maintaining the temperature between −40° C. to 30° C
  10. stirringThe mixture was stirred for 1 hour
  11. temperatureThe reaction mixture was warmed to 22° C.
  12. filtrationfiltered
  13. customdried

Sources & evidence

ORD record
ord-37f5d59ce2c148e49b1e457145e14326
Source dataset
uspto-grants-2006_10
Patent number
US07129350B2

Reaction notes

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