Ethyl Acetate → Biphenyl-2-ylcarbamic Acid 1-(2-{[4-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenylcarbamoyl)-butyl]methylcarbamoyl}ethyl)piperidin-4-yl Ester Dihydrofluoric Acid Salt

HRID 2366337Notes

Reaction equation

HRID 2366337 reaction equation
[Si]([O:8][C@H:9]([C:54]1[CH:63]=[CH:62][C:61]([OH:64])=[C:60]2[C:55]=1[CH:56]=[CH:57][C:58](=[O:65])[NH:59]2)[CH2:10][NH:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([NH:19][C:20]([CH2:22][CH2:23][CH2:24][CH2:25][N:26]([CH3:53])[C:27]([CH2:29][CH2:30][N:31]2[CH2:36][CH2:35][CH:34]([O:37][C:38](=[O:52])[NH:39][C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=3[C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)[CH2:33][CH2:32]2)=[O:28])=[O:21])=[CH:15][CH:14]=1)(C(C)(C)C)(C)C.[FH:66].F.F.C(N(CC)CC)C.CCOC(C)=O>C(Cl)Cl.CN(C=O)C>[FH:66].[FH:66].[OH:8][C@H:9]([C:54]1[CH:63]=[CH:62][C:61]([OH:64])=[C:60]2[C:55]=1[CH:56]=[CH:57][C:58](=[O:65])[NH:59]2)[CH2:10][NH:11][CH2:12][C:13]1[CH:14]=[CH:15][C:16]([NH:19][C:20]([CH2:22][CH2:23][CH2:24][CH2:25][N:26]([CH3:53])[C:27]([CH2:29][CH2:30][N:31]2[CH2:36][CH2:35][CH:34]([O:37][C:38](=[O:52])[NH:39][C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=3[C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)[CH2:33][CH2:32]2)=[O:28])=[O:21])=[CH:17][CH:18]=1

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 175505N,N-Diethylethanamine trihydrofluorideHCID 86646965Biphenyl-2-ylcarbamic Acid 1-(2-{[4-(4-{[(R)-2-(tert-butyldimethyl-silanyloxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-phenylcarbamoyl)butyl]methylcarbamoyl}ethyl)piperidin-4-yl Ester

Product 1

HCID 66831448Biphenyl-2-ylcarbamic Acid 1-(2-{[4-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenylcarbamoyl)-butyl]methylcarbamoyl}ethyl)piperidin-4-yl Ester Dihydrofluoric Acid SaltYield 105.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-{[(R)-2-(tert-butyldimethylsilanyloxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]-methyl}phenylcarbamoyl)butyl]methylcarbamoyl}ethyl)piperidin-4-yl ester (3.87 g, 4.28 mmol) in a mixture of DCM (20 mL) and DMF (2.5 mL) was added triethylamine trihydrofluoride (2.1 mL, 13 mmol). The resulting mixture was stirred at room temperature overnight. DCM (68 mL) was added to the reaction mixture and then, with stirring, EtOAc (68 mL) was added dropwise. A light colored precipitate formed resulting in a slurry. The slurry mixture was filtered through a medium porosity fritted glass filter and the filter cake was rinsed with EtOAc (2×10 mL) and then pressed dry on a nitrogen press to give the title compound (3.73 g, 99% yield).

Workup

  1. stirringwith stirring
  2. customformed
  3. customresulting in a slurry
  4. filtrationThe slurry mixture was filtered through a medium porosity fritted glass
  5. filtrationfilter
  6. washthe filter cake was rinsed with EtOAc (2×10 mL)
  7. custompressed dry on a nitrogen press

Sources & evidence

ORD record
ord-4f42411aaed94db4bc0dc82f39fa3226
Source dataset
uspto-grants-2014_04
Patent number
US08697724B2

Reaction notes

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