Lithium Hydroxide → (R)-1-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-2-(1'-carboxymethyl-4,4'-bipiperidinyl-1-yl)-2-oxo-ethyl 4-(7-methoxy-2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

HRID 2106535Notes

Reaction equation

HRID 2106535 reaction equation
[Li+].[OH-].[CH3:3][O:4][C:5]1[CH:6]=[CH:7][C:8]2[NH:14][C:13](=[O:15])[N:12]([CH:16]3[CH2:21][CH2:20][N:19]([C:22]([O:24][C@H:25]([CH2:46][C:47]4[CH:52]=[C:51]([C:53]([F:56])([F:55])[F:54])[C:50]([NH2:57])=[C:49]([Cl:58])[CH:48]=4)[C:26]([N:28]4[CH2:33][CH2:32][CH:31]([CH:34]5[CH2:39][CH2:38][N:37]([CH2:40][C:41]([O:43]CC)=[O:42])[CH2:36][CH2:35]5)[CH2:30][CH2:29]4)=[O:27])=[O:23])[CH2:18][CH2:17]3)[CH2:11][CH2:10][C:9]=2[CH:59]=1>O.C1COCC1.C(#N)C>[CH3:3][O:4][C:5]1[CH:6]=[CH:7][C:8]2[NH:14][C:13](=[O:15])[N:12]([CH:16]3[CH2:17][CH2:18][N:19]([C:22]([O:24][C@H:25]([CH2:46][C:47]4[CH:52]=[C:51]([C:53]([F:56])([F:54])[F:55])[C:50]([NH2:57])=[C:49]([Cl:58])[CH:48]=4)[C:26]([N:28]4[CH2:33][CH2:32][CH:31]([CH:34]5[CH2:39][CH2:38][N:37]([CH2:40][C:41]([OH:43])=[O:42])[CH2:36][CH2:35]5)[CH2:30][CH2:29]4)=[O:27])=[O:23])[CH2:20][CH2:21]3)[CH2:11][CH2:10][C:9]=2[CH:59]=1

Participants

6

Reactant 2

HCID 3939Lithium Hydroxide2×HCID 16045966(R)-1-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-2-(1'-ethoxycarbonyl methyl-4,4'-bipiperidinyl-1-yl)-2-oxo-ethyl 4-(7-methoxy-2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

Product 1

HCID 57807665(R)-1-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-2-(1'-carboxymethyl-4,4'-bipiperidinyl-1-yl)-2-oxo-ethyl 4-(7-methoxy-2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolvent3×HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1 mg (0.04 mmol) LiOH in 1 mL water was added to a solution of 20 mg (0.02 mmol) (R)-1-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-2-(1′-ethoxycarbonyl methyl-4,4′-bipiperidinyl-1-yl)-2-oxo-ethyl 4-(7-methoxy-2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate in 1 mL THF and the reaction mixture was stirred overnight at RT. To complete the reaction a solution of 1 mg LiOH in 1 mL water was again added and the mixture was stirred for another 3 h at RT. The solvents were eliminated in a nitrogen stream, the residue was taken up in a mixture of acetonitrile and water and the product was subjected to freeze-drying.

Workup

  1. additionwas again added
  2. stirringthe mixture was stirred for another 3 h at RT
  3. customto freeze-drying

Sources & evidence

ORD record
ord-da543d9b9a06450cba0718e525ad207c
Source dataset
uspto-grants-2009_08
Patent number
US07579341B2

Reaction notes

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