Sodium Hydroxide → Biphenyl-2-ylcarbamic Acid 1-(2-{[4-(4-[{(R)-2-(tert-butyldimethyl-silanyloxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)-ethylamino]methyl}-2,5-dimethylphenylcarbamoyl)butyl]methylcarbamoyl}ethyl)piperidin-4-yl Ester

HRID 2412279Notes

Reaction equation

HRID 2412279 reaction equation
[CH:1]([C:3]1[C:8]([CH3:9])=[CH:7][C:6]([NH:10][C:11]([CH2:13][CH2:14][CH2:15][CH2:16][N:17]([CH3:44])[C:18]([CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][CH:25]([O:28][C:29](=[O:43])[NH:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=3[C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[CH2:24][CH2:23]2)=[O:19])=[O:12])=[C:5]([CH3:45])[CH:4]=1)=O.C(O)(=O)C.[NH2:50][CH2:51][C@@H:52]([C:61]1[CH:70]=[CH:69][C:68]([OH:71])=[C:67]2[C:62]=1[CH:63]=[CH:64][C:65](=[O:72])[NH:66]2)[O:53][Si:54]([C:57]([CH3:60])([CH3:59])[CH3:58])([CH3:56])[CH3:55].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>C(Cl)Cl.CO>[C:57]([Si:54]([CH3:56])([CH3:55])[O:53][C@H:52]([C:61]1[CH:70]=[CH:69][C:68]([OH:71])=[C:67]2[C:62]=1[CH:63]=[CH:64][C:65](=[O:72])[NH:66]2)[CH2:51][NH:50][CH2:1][C:3]1[C:8]([CH3:9])=[CH:7][C:6]([NH:10][C:11]([CH2:13][CH2:14][CH2:15][CH2:16][N:17]([CH3:44])[C:18]([CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][CH:25]([O:28][C:29](=[O:43])[NH:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=3[C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[CH2:24][CH2:23]2)=[O:19])=[O:12])=[C:5]([CH3:45])[CH:4]=1)([CH3:60])([CH3:59])[CH3:58]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 666722995-[(R)-2-amino-1-(tert-butyldimethylsilanyloxy)ethyl]-8-hydroxy-1H-quinolin-2-one acetateHCID 86646967Biphenyl-2-ylcarbamic Acid 1-(2-{[4-(4-Formyl-2,5-dimethylphenylcarbamoyl)butyl]methylcarbamoyl}ethyl)piperidin-4-yl Ester

Product 1

HCID 86646968Biphenyl-2-ylcarbamic Acid 1-(2-{[4-(4-[{(R)-2-(tert-butyldimethyl-silanyloxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)-ethylamino]methyl}-2,5-dimethylphenylcarbamoyl)butyl]methylcarbamoyl}ethyl)piperidin-4-yl EsterYield 60.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent3×

Procedure

To the stirred solution of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-formyl-2,5-dimethylphenyl carbamoyl)butyl]methylcarbamoyl}ethyl)piperidin-4-yl ester (˜0.748 mmol) in DCM from the previous reaction was added 5-[(R)-2-amino-1-(tert-butyl-dimethylsilanyloxy)ethyl]-8-hydroxy-1H-quinolin-2-one acetic acid salt (0.295 g, 0.748 mmol) in 1:1 MeOH:DCM (3.0 mL). The resulting mixture was stirred at room temperature for 30 min and then sodium triacetoxyborohydride (0.476 g, 2.24 mmol) was added and stirring was continued at room temperature for 4 h. Aqueous NaOH (1 M, 3 mL) and DCM (3 mL) were added and the layers were separated. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (0-15% MeOH in DCM) to give the title compound (420 mg, 60% yield) as a yellow solid.

Workup

  1. stirringstirring
  2. waitwas continued at room temperature for 4 h
  3. customthe layers were separated
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel flash chromatography (0-15% MeOH in DCM)

Sources & evidence

ORD record
ord-1ba797d39818479984e19861828d137b
Source dataset
uspto-grants-2014_08
Patent number
US08816088B2

Reaction notes

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