Lithium Hydroxide → (S)-4-{(R)-3-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carbonyloxy]-propionyl}-1-(1-methyl-piperidin-4-yl)-piperazine-2-carboxylic acid

HRID 2106546Notes

Reaction equation

HRID 2106546 reaction equation
[Li+].[OH-].[NH2:3][C:4]1[C:9]([C:10]([F:13])([F:12])[F:11])=[CH:8][C:7]([CH2:14][C@@H:15]([O:36][C:37]([N:39]2[CH2:44][CH2:43][CH:42]([N:45]3[CH2:51][CH2:50][C:49]4[CH:52]=[CH:53][CH:54]=[CH:55][C:48]=4[NH:47][C:46]3=[O:56])[CH2:41][CH2:40]2)=[O:38])[C:16]([N:18]2[CH2:23][CH2:22][N:21]([CH:24]3[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]3)[C@H:20]([C:31]([O:33]CC)=[O:32])[CH2:19]2)=[O:17])=[CH:6][C:5]=1[Cl:57]>C1COCC1>[NH2:3][C:4]1[C:9]([C:10]([F:11])([F:13])[F:12])=[CH:8][C:7]([CH2:14][C@@H:15]([O:36][C:37]([N:39]2[CH2:40][CH2:41][CH:42]([N:45]3[CH2:51][CH2:50][C:49]4[CH:52]=[CH:53][CH:54]=[CH:55][C:48]=4[NH:47][C:46]3=[O:56])[CH2:43][CH2:44]2)=[O:38])[C:16]([N:18]2[CH2:23][CH2:22][N:21]([CH:24]3[CH2:25][CH2:26][N:27]([CH3:30])[CH2:28][CH2:29]3)[C@H:20]([C:31]([OH:33])=[O:32])[CH2:19]2)=[O:17])=[CH:6][C:5]=1[Cl:57]

Participants

4

Reactant 2

HCID 3939Lithium Hydroxide2×HCID 57807704Ethyl (S)-4-{(R)-3-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carbonyloxy]-propionyl}-1-(1-methyl-piperidin-4-yl)-piperazine-2-carboxylate

Product 1

HCID 57807525(S)-4-{(R)-3-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carbonyloxy]-propionyl}-1-(1-methyl-piperidin-4-yl)-piperazine-2-carboxylic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

0.26 mL (0.13 mmol) 0.5 M LiOH solution were added to 50.0 mg (0.06 mmol) ethyl(S)-4-{(R)-3-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carbonyloxy]-propionyl}-1-(1-methyl-piperidin-4-yl)-piperazine-2-carboxylate in 0.8 mL THF and the reaction mixture was stirred overnight at RT. To complete the reaction another 50 μL (0.1 mmol) 0.5 M LiOH solution were added, it was stirred for another 4 h at RT and then the reaction mixture was purified by HPLC without working up; the fractions containing the product were combined and lyophilised.

Workup

  1. additionwere added
  2. stirringit was stirred for another 4 h at RT
  3. customthe reaction mixture was purified by HPLC
  4. additionthe fractions containing the product

Sources & evidence

ORD record
ord-c28e55d8f2c24501b1cb323c8bd3be0d
Source dataset
uspto-grants-2009_08
Patent number
US07579341B2

Reaction notes

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