Sodium Acetate → 9-tert-butyl-3-methoxy-2-bromo-14-(1,3-thiazol-5-yl)-5,6,10,11,12,13-hexahydroazocino[4',3':4,5]pyrrolo[2,1-a]isoquinolin-8(9H)-one

HRID 1971726Notes

Reaction equation

HRID 1971726 reaction equation
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][N:8]([C:15](=O)[C:16]([N:18]([C:30]([CH3:33])([CH3:32])[CH3:31])[CH2:19][CH2:20][CH2:21][CH2:22][C:23]#[C:24][C:25]3[S:29][CH:28]=[N:27][CH:26]=3)=[O:17])[CH:9]2C(O)=O)=[CH:4][C:3]=1[O:35][CH3:36].C([O-])(=O)C.[Na+].CCOCC.CCCCCCC>C(OC(=O)C)(=O)C.O>[C:30]([N:18]1[CH2:19][CH2:20][CH2:21][CH2:22][C:23]2[C:24]([C:25]3[S:29][CH:28]=[N:27][CH:26]=3)=[C:9]3[C:10]4[CH:11]=[C:2]([Br:1])[C:3]([O:35][CH3:36])=[CH:4][C:5]=4[CH2:6][CH2:7][N:8]3[C:15]=2[C:16]1=[O:17])([CH3:31])([CH3:33])[CH3:32]

Participants

6

Reactant 3

HCID 517045Sodium AcetateHCID 21897273Diethylether heptaneHCID 58124897HCID 58124897, compound

Product 1

HCID 581247959-tert-butyl-3-methoxy-2-bromo-14-(1,3-thiazol-5-yl)-5,6,10,11,12,13-hexahydroazocino[4',3':4,5]pyrrolo[2,1-a]isoquinolin-8(9H)-oneYield 43.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 7918Acetic AnhydrideSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of 220 mg of 17h and 150 mg of sodium acetate in 15 ml of acetic anhydride was stirred at 105° C. for 45 min. The reaction mixture was cooled, diluted with 60 ml of water and stirred at ambient temperature for 1 hr to destroy excess anhydride. The aqueous material was then neutralized by careful addition of cold con. aq. NH4OH. The product was extracted with ethyl acetate. The extract was washed with water, dried, concentrated and the material isolated was chromatographed over silica gel using a gradient of heptane/ethyl acetate as eluent. The material isolated was treated with ether/heptane, to give 85 mg of 17i as white crystals. MS-ESI: [M+1] 514.11 and 516.11.

Workup

  1. temperatureThe reaction mixture was cooled
  2. stirringstirred at ambient temperature for 1 hr
  3. customto destroy excess anhydride
  4. additionThe aqueous material was then neutralized by careful addition of cold con
  5. extractionThe product was extracted with ethyl acetate
  6. washThe extract was washed with water
  7. customdried
  8. concentrationconcentrated
  9. customthe material isolated
  10. customwas chromatographed over silica gel using a gradient of heptane/ethyl acetate as eluent
  11. customThe material isolated

Sources & evidence

ORD record
ord-8f7981b111644077ae5b95d5451de637
Source dataset
uspto-grants-2013_04
Patent number
US08431564B2

Reaction notes

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