Butyl Acetate → HCID 9804315, compound

HRID 459839Notes

Reaction equation

HRID 459839 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:28][CH3:29])=[C:17]([O:20][CH2:21][CH2:22][NH:23][CH2:24][C@@H:25]([OH:27])[CH3:26])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8].C(N(C(C)C)C(C)C)C.Br[CH2:40][C:41](OC)=[O:42].C(OCCCC)(=O)C>CN1CCCC1=O.O>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:28][CH3:29])=[C:17]([O:20][CH2:21][CH2:22][N:23]4[CH2:24][C@H:25]([CH3:26])[O:27][C:41](=[O:42])[CH2:40]4)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

7

Reactant 4

HCID 31272Butyl AcetateHCID 60984Methyl bromoacetateHCID 81531DiisopropylethylamineHCID 11270115HCID 11270115, compound

Product 1

HCID 9804315HCID 9804315, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
-10 °C

Procedure

425 g of (S)-4-[(3-chloro-4-fluoro-phenyl)amino]-6-{2-[(2-hydroxypropyl)amino]ethyloxy}-7-methoxy-quinazoline and 210 ml N-ethyl-diisopropylamine are dissolved in 640 ml N-methylpyrrolidone. After the addition of 105 ml methyl bromoacetate the mixture is stirred for 1 hour at 20–25° C. After the addition of 8500 ml n-butyl acetate and 4300 ml of water the phases are separated and the organic phase is washed with 4300 ml of water. The organic phase is evaporated down at 200 mbar to 50% of the original volume and 4300 ml of n-butyl acetate are added. The mixture is heated to 120–130° C. for 40 hours, filtered and evaporated down to a volume of 2000 ml at 200 mbar. After cooling to −10° C. the precipitate is suction filtered, washed with 800 ml n-butyl acetate and dried at 50° C. The crude product is recrystallised twice from methylethylketone (3750 and 5100 ml).

Workup

  1. customare separated
  2. washthe organic phase is washed with 4300 ml of water
  3. customThe organic phase is evaporated down at 200 mbar to 50% of the original volume and 4300 ml of n-butyl acetate
  4. additionare added
  5. temperatureThe mixture is heated to 120–130° C. for 40 hours
  6. filtrationfiltered
  7. customevaporated down to a volume of 2000 ml at 200 mbar
  8. filtrationfiltered
  9. washwashed with 800 ml n-butyl acetate
  10. customdried at 50° C
  11. customThe crude product is recrystallised twice from methylethylketone (3750 and 5100 ml)

Sources & evidence

ORD record
ord-88f191b5cba34cd9af997df9dc0b6513
Source dataset
uspto-grants-2007_03
Patent number
US07196091B2

Reaction notes

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