Hydrochloric Acid → Oliceridine hydrochloride

HRID 626494노트

반응식

HRID 626494 반응식
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C@@:7]1([CH2:17][CH2:18][NH2:19])[CH2:16][C:11]2([CH2:15][CH2:14][CH2:13][CH2:12]2)[O:10][CH2:9][CH2:8]1.S([O-])([O-])(=O)=O.[Na+].[Na+].[CH3:27][O:28][C:29]1[CH:33]=[CH:32][S:31][C:30]=1[CH:34]=O.[BH4-].[Na+].[ClH:38]>CCOCC.CO.C(Cl)Cl>[ClH:38].[CH3:27][O:28][C:29]1[CH:33]=[CH:32][S:31][C:30]=1[CH2:34][NH:19][CH2:18][CH2:17][C@:7]1([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)[CH2:16][C:11]2([CH2:15][CH2:14][CH2:13][CH2:12]2)[O:10][CH2:9][CH2:8]1

참가 물질

9

반응물 5

HCID 313Hydrochloric AcidHCID 24436Sodium SulfateHCID 5883153-Methoxythiophene-2-carbaldehydeHCID 4311764Sodium borohydrideHCID 68314401Trv-0109662

생성물 1

HCID 68313941Oliceridine hydrochloride수율 41%

시약·촉매·용매 3

HCID 887Methanol용매HCID 3283Diethyl Ether용매HCID 6344Dichloromethane용매

실험 절차

Into a vial were added 2-[(9R)-9-(Pyridin-2-yl)-6-oxaspiro[4.5]decan-9-yl]ethan-1-amine (500 mg, 1.92 mmole), 18 mL CH2Cl2 and sodium sulfate (1.3 g, 9.6 mmole). The 3-methoxythiophene-2-carboxaldehyde (354 mg, 2.4 mmole) was then added, and the misture was stirred overnight. NaBH4 (94 mg, 2.4 mmole) was added to the reaction mixture, stirred for 10 minutes, and then MeOH (6.0 mL) was added, stirred 1 h, and finally quenched with water. The organics were separated off and evaporated. The crude residue was purified by a Gilson prep HPLC. The desired fractions collected and concentrated and lyophilized. After lyophilization, residue was partitioned between CH2Cl2 and 2N NaOH, and the organic layers were collected. After solvent was concentrated to half of the volume, 1.0 eq of 1N HCl in Et2O was added, and majority of solvent evaporated under reduced pressure. The solid obtained was washed several times with Et2O and dried to provide [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5]decan-9-yl]ethyl})amine monohydrochloride (336 mg, 41% yield, m/z 387.0 [M+H]+ observed) as a white solid. The NMR for Compound 140 is described herein.

후처리

  1. stirringstirred for 10 minutes
  2. stirringstirred 1 h
  3. customfinally quenched with water
  4. customThe organics were separated off
  5. customevaporated
  6. customThe crude residue was purified by a Gilson prep HPLC
  7. customThe desired fractions collected
  8. concentrationconcentrated
  9. customAfter lyophilization, residue was partitioned between CH2Cl2 and 2N NaOH
  10. customthe organic layers were collected
  11. additionwas added
  12. custommajority of solvent evaporated under reduced pressure
  13. customThe solid obtained
  14. washwas washed several times with Et2O
  15. customdried

출처 및 근거

ORD 기록
ord-015e9808b28c4c9f9ed739fbee648d73
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09309234B2

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