Ammonia → Bopindolol

HRID 1759303Notes

Reaction equation

HRID 1759303 reaction equation
[C:1]([OH:9])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:10]([NH:14][CH2:15][CH:16](O)[CH2:17][O:18][C:19]1[CH:27]=[CH:26][CH:25]=[C:24]2[C:20]=1[CH:21]=[C:22]([CH3:28])[NH:23]2)([CH3:13])([CH3:12])[CH3:11].C(OC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.N.C(O)(=O)/C=C/C(O)=O.C(O)(=O)/C=C/C([O-])=O>CN(C)P(=O)(N(C)C)N(C)C.CC(C)=O.CO.CCOCC>[C:1]([O:9][CH:16]([CH2:15][NH:14][C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:17][O:18][C:19]1[CH:27]=[CH:26][CH:25]=[C:24]2[C:20]=1[CH:21]=[C:22]([CH3:28])[NH:23]2)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

11

Reactant 6

HCID 222AmmoniaHCID 243Benzoic AcidHCID 7167Benzoic anhydrideHCID 1526621-(tert-Butylamino)-3-[(2-methyl-1H-indol-4-yl)oxy]propan-2-olHCID 444972Fumaric AcidHCID 6183479Fumarate(1-)

Product 1

HCID 44112Bopindolol

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 12679HexamethylphosphoramideSolvent

Procedure

26 g of Benzoic acid are dissolved, while heating, in 50 cc of hexamethylphosphoric acid triamide and 3.5 g of 1-tert.butylamino-3-(2-methyl-indole-4-yloxy)-2-propanol are added. After cooling, 3.0 g of benzoic acid anhydride are added and stirring is effected for 20 hours at room temperature. The resulting clear, yellow solution is poured onto ice, 0.5 liters of ether are added and stirring is effected for 2 hours. After making the liquid alkaline with concentrated ammonia, the ether phase is separated, shaken out with tartaric acid, made alkaline with caustic soda solution while cooling with ice and extracted with methylene chloride. After evaporating the solvent, the residue is crystallised with 1 mol of fumaric acid from methanol and acetone. M.p. of hydrogen fumarate form: 189°-191°.

Workup

  1. temperatureAfter cooling
  2. additionare added
  3. stirringstirring
  4. waitis effected for 2 hours
  5. customthe ether phase is separated
  6. stirringshaken out with tartaric acid
  7. temperaturewhile cooling with ice
  8. extractionextracted with methylene chloride
  9. customAfter evaporating the solvent
  10. custom189°-191°

Sources & evidence

ORD record
ord-f5b2ef7fa75b4d2889e01a800a10038e
Source dataset
uspto-grants-1982_07
Patent number
US04340541

Reaction notes

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