Hydrochloric Acid → Oliceridine hydrochloride

HRID 626494Notes

Reaction equation

HRID 626494 reaction equation
[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

Participants

9

Reactant 5

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

Product 1

HCID 68313941Oliceridine hydrochlorideYield 41%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-015e9808b28c4c9f9ed739fbee648d73
Source dataset
uspto-grants-2016_04
Patent number
US09309234B2

Reaction notes

Loading…