Codeine → HCID 66791479, compound

HRID 1096592Notes

Reaction equation

HRID 1096592 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([C:7]2[NH:11][C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[N:8]=2)[CH2:2]1.[Br:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][C@@H:24]([NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:25][C:26](O)=[O:27])=[CH:19][CH:18]=1.CN1[C@@H]2CC3C=CC(OC)=C4O[C@H]5[C@@H](O)C=C[C@@H]2[C@]5(C=34)CC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[NH:11]1[C:10]2[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=2[N:8]=[C:7]1[C@@H:3]1[CH2:4][CH2:5][CH2:6][N:1]([C:26](=[O:27])[CH2:25][C@H:24]([NH:29][C:30](=[O:31])[O:32][C:33]([CH3:34])([CH3:35])[CH3:36])[CH2:23][C:20]2[CH:19]=[CH:18][C:17]([Br:16])=[CH:22][CH:21]=2)[CH2:2]1

Participants

7

Reactant 4

HCID 5284371CodeineHCID 7009737(3R)-4-(4-bromophenyl)-3-{[(tert-butoxy)carbonyl]amino}butanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 40429354HCID 40429354, compound

Product 1

HCID 66791479HCID 66791479, compoundYield 75.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

(R)-2-(Piperidin-3-yl)-1H-benzo[d]imidazole (5A) (0.29 mmol, 58 mg) in DMF (15 mL) was added (R)-4-(4-bromophenyl)-3-(tert-butoxycarbonylamino)butanoic acid (0.32 mmol, 115 mg) and N-methylmorphine (1.16 mmol, 0.13 mL). The reaction mixture was stirred at rtfor 5 min and then added HATU (0.32 mmol, 122 mg) and kept stirring at rt overnight. The reaction mixture was poured into H2O, extracted with EtOAc. The extract was washed with H2O, brine, dried over MgSO4 and filtered. The filtrate was concentrated in vacuo and purified by preparative LC/MS (35-60% CH3CN in H2O) to afford tert-butyl (R)-4-((R)-3-(1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-1-(4-bromophenyl)-4-oxobutan-2-ylcarbamate (5B) (0.22 mmol, 120 mg, two-step yield: 75.9%). ESI-MS: m/z 542.3 (M+H)+.

Workup

  1. extractionextracted with EtOAc
  2. washThe extract was washed with H2O, brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. custompurified by preparative LC/MS (35-60% CH3CN in H2O)

Sources & evidence

ORD record
ord-bdaf1830fb0d48f18b3b2f3d1f449c63
Source dataset
uspto-grants-2012_03
Patent number
US08138168B1

Reaction notes

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