Isopropyl Acetate → HCID 12332319, compound

HRID 500983Notes

Reaction equation

HRID 500983 reaction equation
[NH2:1][C:2]([CH3:6])([CH3:5])[CH2:3][OH:4].CC(C)([O-])C.[K+].F[C:14]1[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=1.C(OC(C)C)(=O)C>O1CCCC1.O>[CH3:5][C:2]([NH2:1])([CH3:6])[CH2:3][O:4][C:14]1[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=1

Participants

7

Reactant 4

HCID 7915Isopropyl AcetateHCID 9590p-FluoronitrobenzeneHCID 118072-Amino-2-methyl-1-propanolHCID 23665647Potassium tert-butoxide

Product 1

HCID 12332319HCID 12332319, compoundYield 118.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
20 °C

Procedure

A solution of 2-amino-2-methyl-1-propanol (488 g, 5.47 mol) in tetrahydrofuran (1.46 L) was added over 35 mins to a solution of potassium tert-butoxide (634 g, 5.65 mol) in tetrahydrofuran (2.95 L) at 2±3° C. The mixture was maintained at this temperature for a further 55 minutes before 4-fluoronitrobenzene (551 mL, 3.90 mol) was added over 1 hour 25 mins keeping the temperature below 10° C. The mixture was warmed to 20±3° C. and stirred for 2 hours. Water (1.95 L) and Isopropyl acetate (1.95 L) were charged to the mixture which was stirred, settled and separated. The organic phase was washed again with water (1.95 L) before 5M hydrochloric acid (1.95 L) was charged, keeping the temperature below 25° C. Isooctane (1.95 L) was added and the layers separated. 5M hydrochloric acid (322 mL) was added to the aqueous phase which was then reduced to approximately 3.9 L by vacuum distillation, causing spontaneous crystallisation, and stirred at room temperature overnight. Filtration, washing with water (2×488 mL) and drying in vacuo at around 48° C. afforded the title intermediate as a white solid (972.1 g, 72% th).

Workup

  1. additionwas added over 1 hour 25 mins
  2. customthe temperature below 10° C
  3. stirringwas stirred
  4. customseparated
  5. washThe organic phase was washed again with water (1.95 L) before 5M hydrochloric acid (1.95 L)
  6. additionwas charged
  7. customthe temperature below 25° C
  8. additionIsooctane (1.95 L) was added
  9. customthe layers separated
  10. addition5M hydrochloric acid (322 mL) was added to the aqueous phase which
  11. distillationwas then reduced to approximately 3.9 L by vacuum distillation
  12. customcrystallisation
  13. stirringstirred at room temperature overnight
  14. filtrationFiltration
  15. washwashing with water (2×488 mL)
  16. customdrying in vacuo at around 48° C.

Sources & evidence

ORD record
ord-9c57db22dcc04ca8a0bb23ccc57b7ecf
Source dataset
uspto-grants-2010_08
Patent number
US07772250B2

Reaction notes

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