Lithium Hydroxide → (R)-1-carboxy-2-(3,5-dibromo-4-hydroxy-phenyl)-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

HRID 1015496Notes

Reaction equation

HRID 1015496 reaction equation
[Li+].[OH-].[O:3]=[C:4]1[N:10]([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C@@H:20]([C:31]([O:33]C)=[O:32])[CH2:21][C:22]3[CH:27]=[C:26]([Br:28])[C:25]([OH:29])=[C:24]([Br:30])[CH:23]=3)=[O:18])[CH2:13][CH2:12]2)[CH2:9][CH2:8][C:7]2[CH:35]=[CH:36][CH:37]=[CH:38][C:6]=2[NH:5]1>C1COCC1>[O:3]=[C:4]1[N:10]([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C@@H:20]([C:31]([OH:33])=[O:32])[CH2:21][C:22]3[CH:27]=[C:26]([Br:28])[C:25]([OH:29])=[C:24]([Br:30])[CH:23]=3)=[O:18])[CH2:13][CH2:12]2)[CH2:9][CH2:8][C:7]2[CH:35]=[CH:36][CH:37]=[CH:38][C:6]=2[NH:5]1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 67302314(R)-2-(3,5-dibromo-4-hydroxy-phenyl)-1-methoxycarbonyl-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

Product 1

HCID 67301880(R)-1-carboxy-2-(3,5-dibromo-4-hydroxy-phenyl)-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 0.51 g (21.3 mmol) LiOH was added to a solution of (R)-2-(3,5-dibromo-4-hydroxy-phenyl)-1-methoxycarbonyl-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate (crude product from Example 128g) in 80 mL THF and the reaction mixture was stirred for 3 h at RT. The THF was eliminated i. vac., the aqueous phase was washed with EtOAc, acidified with 10% HCl and the aqueous phase was extracted exhaustively with EtOAc. The combined organic phases were evaporated down i.vac., suspended in diethyl ether, filtered, the residue was dried and then purified by chromatography (silica gel, DCM/MeOH/AcOH 90:10:1).

Workup

  1. wash, the aqueous phase was washed with EtOAc
  2. extractionthe aqueous phase was extracted exhaustively with EtOAc
  3. customThe combined organic phases were evaporated down i.vac
  4. filtrationfiltered
  5. customthe residue was dried
  6. custompurified by chromatography (silica gel, DCM/MeOH/AcOH 90:10:1)

Sources & evidence

ORD record
ord-2e9a1715f5b748ca8e721d472797a351
Source dataset
uspto-grants-2011_07
Patent number
US07985747B2

Reaction notes

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