Hydrochloric Acid → Mabuterol hydrochloride

HRID 1111934Notes

Reaction equation

HRID 1111934 reaction equation
Cl.[NH2:2][C:3]1[C:8]([C:9]([F:12])([F:11])[F:10])=[CH:7][C:6]([C:13](=[O:20])[CH2:14][NH:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[CH:5][C:4]=1[Cl:21].[BH4-].[Na+].Cl>CO>[ClH:21].[NH2:2][C:3]1[C:8]([C:9]([F:10])([F:11])[F:12])=[CH:7][C:6]([CH:13]([OH:20])[CH2:14][NH:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[CH:5][C:4]=1[Cl:21]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 22765862HCID 22765862, compound

Product 1

HCID 6917754Mabuterol hydrochloride

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
-15 °C

Procedure

80 gm of 4'-amino-2-tert.butylamino-3'-chloro-5'-trifluoromethyl-acetophenone hydrochloride (decomposition between 223° and 231° C.) were dissolved in 500 ml of methanol, and the solution was cooled to -15° C. 9.5 gm of sodium borohydride were added in small portions over a period of one hour, while stirring and maintaining the temperature between -5° to -15° C. After one hour more of stirring at -15° C., the mixture was acidified with 2N hydrochloric acid, and the methanol was removed in vacuo. The remaining aqueous solution was made alkaline with 2N ammonia and was then extracted with ethyl acetate. The organic layer was washed with water, dried, and 50 ml of 4.5N isopropanolic hydrochloric acid were added. The precipitated hydrochloride of the above-mentioned substance was suction-filtered off and washed with ethyl acetate and ether. M.p. 205°-207° C. (decomp.). By concentration of the filtrate a further amount of the product was obtained.

Workup

  1. temperaturemaintaining the temperature between -5° to -15° C
  2. stirringAfter one hour more of stirring at -15° C.
  3. customthe methanol was removed in vacuo
  4. extractionwas then extracted with ethyl acetate
  5. washThe organic layer was washed with water
  6. customdried
  7. addition50 ml of 4.5N isopropanolic hydrochloric acid were added
  8. filtrationThe precipitated hydrochloride of the above-mentioned substance was suction-filtered off
  9. washwashed with ethyl acetate and ether
  10. customBy concentration of the filtrate a further amount of the product was obtained

Sources & evidence

ORD record
ord-7ede3d4e360f47b9b48ad6283794b458
Source dataset
uspto-grants-1978_10
Patent number
US04119710

Reaction notes

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