Codeine → HCID 66791560, compound

HRID 1096594

Reaction equation

HRID 1096594 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[N:8]=[C:7]1[C@@H:15]1[CH2:20][CH2:19][CH2:18][NH:17][CH2:16]1.[Br:21][C:22]1[CH:27]=[CH:26][C:25]([CH2:28][C@@H:29]([NH:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:30][C:31](O)=[O:32])=[CH:24][CH:23]=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>[Br:21][C:22]1[CH:27]=[CH:26][C:25]([CH2:28][C@@H:29]([NH:34][C:35](=[O:36])[O:37][C:38]([CH3:40])([CH3:39])[CH3:41])[CH2:30][C:31]([N:17]2[CH2:18][CH2:19][CH2:20][C@@H:15]([C:7]3[N:6]([CH2:5][CH2:4][CH2:3][O:2][CH3:1])[C:10]4[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=4[N:8]=3)[CH2:16]2)=[O:32])=[CH:24][CH:23]=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 66785056HCID 66785056, compound

Product 1

HCID 66791560HCID 66791560, compoundYield 89.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

(R)-1-(3-Methoxypropyl)-2-(piperidin-3-yl)-1H-benzo[d]imidazole (0.29 mmol, 79 mg) in DMF (15 mL) was added to (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 rt for 5 min and then added HATU (0.32 mmol, 122 mg) and kept stifling 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)-1-(4-bromophenyl)-4-((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-4-oxobutan-2-ylcarbamate (6A) (0.26 mmol, 160 mg, yield: 89.7%). ESI-MS: m/z 614.4 (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-5819837bf54c4d89bb07582854f3e4f8
Source dataset
uspto-grants-2012_03
Patent number
US08138168B1

Linked notes

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