Hydrochloric Acid → Levalbuterol Hydrochloride

HRID 1078016

반응식

HRID 1078016 반응식
[H][H].[CH3:3][C:4]([NH:7][CH2:8][CH:9]([OH:19])[C:10]1[CH:11]=[CH:12][C:13]([OH:18])=[C:14]([CH2:16][OH:17])[CH:15]=1)([CH3:6])[CH3:5].[ClH:20].CCOCC>C(O)C.[Pd].C(OC)(C)(C)C>[CH3:6][C:4]([NH:7][CH2:8][C@H:9]([OH:19])[C:10]1[CH:11]=[CH:12][C:13]([OH:18])=[C:14]([CH2:16][OH:17])[CH:15]=1)([CH3:3])[CH3:5].[ClH:20]

참가 물질

8

반응물 4

HCID 313Hydrochloric AcidHCID 2083SalbutamolHCID 3283Diethyl EtherHCID 178418361HCID 178418361, 화합물

생성물 1

HCID 123601Levalbuterol Hydrochloride수율 83.5%

시약·촉매·용매 3

HCID 23938Palladium촉매HCID 702Ethanol용매2회HCID 15413tert-Butyl methyl ether용매

실험 절차

A mixture of (R)-4-benzyl albuterol from Example-3 (6.6 g, 20 mmol) and 10% Pd/C (1.32 g) in 50 mL of ethanol (denatured with 5 vol % 2-propanol) is shaken on a Parr-hydrogenator under 50 psi of hydrogen at room temperature for 2-3 hours. The catalyst is removed by filtration and the filtrate is concentrated to give crude (R)-albuterol (compound IIIa). The crude albuterol (20 mmol) is dissolved in 20 mL of ethanol and treated with anhydrous HCl in ether (1.0M, 19 mL, 0.95 eq) at 0°-5° C. After 30 min at room temperature, 20 mL of methyl t-butyl ether (MTBE) is added to the mixture and the resulting mixture is stirred at room temperature for 30 min and at 0°-5° C. for 2 hours. The white solid (R)-albuterol hydrochloride (compound IIIb) is collected by filtration and recrystallized from 52 mL of ethanol and 26 mL of MTBE to give pure (R)-albuterol hydrochloride as a white powder (4.6 g, 83.5% yield, 99.6% ee, 99.3% purity).

후처리

  1. customThe catalyst is removed by filtration
  2. concentrationthe filtrate is concentrated
  3. customto give crude (R)-albuterol (compound IIIa)
  4. filtrationThe white solid (R)-albuterol hydrochloride (compound IIIb) is collected by filtration
  5. customrecrystallized from 52 mL of ethanol and 26 mL of MTBE

출처 및 근거

ORD 기록
ord-9938fa9dfa0b4e92a8f4d45e9ca54432
출처 데이터셋
uspto-grants-1996_08
특허 번호
US05545745

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