Toluene → HCID 23441203, compound

HRID 2119335Notes

Reaction equation

HRID 2119335 reaction equation
Cl[CH2:2][C:3]([OH:5])=[O:4].Cl[CH2:7][C:8]([N:10]([C:12]1[CH:17]=[C:16]([CH2:18][N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)[CH:15]=[CH:14][C:13]=1[NH:25][C:26](=O)CCl)[CH3:11])=[O:9].[OH-:30].[Na+].[Cl-].[NH4+].[C:34]1([CH3:40])C=CC=CC=1.[CH2:41]1[CH2:45][O:44][CH2:43]C1>O>[CH3:11][N:10]1[C:12]2[C:13](=[CH:14][CH:15]=[C:16]([CH2:18][N:19]3[CH2:20][CH2:21][O:22][CH2:23][CH2:24]3)[CH:17]=2)[N:25]([CH:26]=[C:2]([C:43]([O:44][CH2:45][CH3:41])=[O:30])[C:3]([O:5][CH2:34][CH3:40])=[O:4])[CH2:7][C:8]1=[O:9]

Participants

7

Reactant 5

HCID 1140TolueneHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 23441205HCID 23441205, compound

Product 1

HCID 23441203HCID 23441203, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
15 °C

Procedure

A solution of 2-chloro-N-[2-[(chloroacetyl)amino]-5-(morpholin-4-ylmethyl)phenyl]-N-methylacetamide chloroacetic acid salt (792 g) in THF (2000 ml) and water (1600 ml) is added aqueous sodium hydroxide (532 g, 50 wt %) while maintaining 13-17° C. via occasional cooling with a dry ice/acetone bath. After 20 min, a solution of ammonium chloride (89 g) in water (400 ml) is added followed by toluene (2000 ml). The phases are separated and the organic is washed with water (100 ml). The combined aqueous are back extracted with a mixture of THF (1000 ml) and toluene (1300 ml). The THF/toluene back extract is washed with water (100 ml). The combined aqueous is back extracted with a mixture of THF (1000 ml) and toluene (1300 ml). The THF/ toluene back extract is washed with water (100 ml). The combined aqueous is back extracted with a mixture of THF (1000 ml) and toluene (1300 ml). The combined organics are concentrated in vacuo. Isopar-H (5.35 liter) and diethyl ethoxymethylenemalonate (394 g) are added and the mixture is warmed to 123° C. with distillation of a small amount of solvent and stirred at 122 to 125° C. for 3 h. The resultant solution is slowly cooled to −2° C. over /2 h to give a slurry. The precipitate is collected by filtration, washed with branched octanes (2 liter) and dried in a nitrogen stream to give a light yellow solid (573 g). Physical characteristics: 1H NMR (400 MHz, CDCl3) δ1.30, 1.35, 2.45, 3.41, 3.50, 3.72, 4.15, 4.23, 4.30, 6.99, 7.07, 7.75; 13C NMR (100 MHz, CDCl3) δ14.14, 14.26, 29.01, 52.09, 53.57, 60.70, 61.26,62.77,66.89, 102.75, 115.50, 119.42, 124.45, 129.12, 131.42, 136.17, 146.18, 164.25, 165.79, 166.24; Anal. Found: C, 61.16; H, 6.91; N, 9.72.

Workup

  1. temperaturevia occasional cooling with a dry ice/acetone bath
  2. customThe phases are separated
  3. washthe organic is washed with water (100 ml)
  4. extractionThe combined aqueous are back extracted with a mixture of THF (1000 ml) and toluene (1300 ml)
  5. extractionThe THF/toluene back extract
  6. washis washed with water (100 ml)
  7. extractionThe combined aqueous is back extracted with a mixture of THF (1000 ml) and toluene (1300 ml)
  8. extractionThe THF/ toluene back extract
  9. washis washed with water (100 ml)
  10. extractionThe combined aqueous is back extracted with a mixture of THF (1000 ml) and toluene (1300 ml)
  11. concentrationThe combined organics are concentrated in vacuo
  12. additionIsopar-H (5.35 liter) and diethyl ethoxymethylenemalonate (394 g) are added
  13. temperaturethe mixture is warmed to 123° C. with distillation of a small amount of solvent
  14. temperatureThe resultant solution is slowly cooled to −2° C. over /2 h
  15. customto give a slurry
  16. filtrationThe precipitate is collected by filtration
  17. washwashed with branched octanes (2 liter)
  18. customdried in a nitrogen stream

Sources & evidence

ORD record
ord-d3c2304444324bb8a3ee012dcbc5d0a1
Source dataset
uspto-grants-2004_02
Patent number
US06686356B2

Reaction notes

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