Potassium Carbonate → (R)-1-(4-benzyloxy-3,5-dimethyl-benzyl)-2-(1'-ethoxycarbonylmethyl-4,4'-bipiperidinyl-1-yl)-2-oxo-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

HRID 730665Notes

Reaction equation

HRID 730665 reaction equation
[N:1]1([CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:6][CH2:5][CH:4]([CH:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH2:3][CH2:2]1.[O:19]=[C:20]1[N:26]([CH:27]2[CH2:32][CH2:31][N:30]([C:33]([O:35][C@@H:36]([C:54](O)=[O:55])[CH2:37][C:38]3[CH:43]=[C:42]([CH3:44])[C:41]([O:45][CH2:46][C:47]4[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=4)=[C:40]([CH3:53])[CH:39]=3)=[O:34])[CH2:29][CH2:28]2)[CH2:25][CH2:24][C:23]2[CH:57]=[CH:58][CH:59]=[CH:60][C:22]=2[NH:21]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(C(C)C)C(C)C)C.C([O-])([O-])=O.[K+].[K+]>C1COCC1.CN(C=O)C>[O:19]=[C:20]1[N:26]([CH:27]2[CH2:32][CH2:31][N:30]([C:33]([O:35][C@H:36]([CH2:37][C:38]3[CH:43]=[C:42]([CH3:44])[C:41]([O:45][CH2:46][C:47]4[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=4)=[C:40]([CH3:53])[CH:39]=3)[C:54]([N:10]3[CH2:11][CH2:12][CH:7]([CH:4]4[CH2:5][CH2:6][N:1]([CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:2][CH2:3]4)[CH2:8][CH2:9]3)=[O:55])=[O:34])[CH2:29][CH2:28]2)[CH2:25][CH2:24][C:23]2[CH:57]=[CH:58][CH:59]=[CH:60][C:22]=2[NH:21]1

Participants

8

Reactant 5

HCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 22945803Ethyl [4,4′-bipiperidine]-1-acetateHCID 25208036(R)-2-(4-benzyloxy-3,5-dimethyl-phenyl)-1-carboxy-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

Product 1

HCID 67273836(R)-1-(4-benzyloxy-3,5-dimethyl-benzyl)-2-(1'-ethoxycarbonylmethyl-4,4'-bipiperidinyl-1-yl)-2-oxo-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

0.99 g (3.90 mmol) ethyl [4,4′]bipiperidinyl-1-yl-acetate were added at RT to a solution of 2.00 g (3.50 mmol) (R)-2-(4-benzyloxy-3,5-dimethyl-phenyl)-1-carboxy-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate (Example 1g), 1.25 g (3.90 mmol) TBTU and 0.67 mL (3.90 mmol) ethyldiisopropylamine in 20 mL THF and 5 mL DMF and the reaction mixture was stirred overnight. 15% K2CO3 solution was added, the mixture was extracted exhaustively with EtOAc, the combined organic phases were washed with saturated NaCl solution and dried on Na2SO4. After the elimination of the desiccant and solvent the product was obtained, which was reacted further without purification.

Workup

  1. extractionthe mixture was extracted exhaustively with EtOAc
  2. washthe combined organic phases were washed with saturated NaCl solution
  3. customdried on Na2SO4
  4. customAfter the elimination of the desiccant and solvent the product was obtained
  5. customwhich was reacted further without purification

Sources & evidence

ORD record
ord-81dd1b89342c4c10a705ca4c973cf962
Source dataset
uspto-grants-2009_09
Patent number
US07582625B2

Reaction notes

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