Lithium hydroxide, monohydrate → HCID 66684917, compound

HRID 579163Notes

Reaction equation

HRID 579163 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][C:12](=[O:14])[N:11]([C:15]2[CH:19]=[C:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[S:17][C:16]=2[C:26]([O:28]C)=[O:27])[C@H:10]([CH:30]2[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.[OH-].[Li+]>C1COCC1.O.CO>[CH:30]1([C@@H:10]2[CH2:9][NH:8][CH2:13][C:12](=[O:14])[N:11]2[C:15]2[CH:19]=[C:18]([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[S:17][C:16]=2[C:26]([OH:28])=[O:27])[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]1.[C:1]([O:5][C:6]([N:8]1[CH2:13][C:12](=[O:14])[N:11]([C:15]2[CH:19]=[C:18]([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[S:17][C:16]=2[C:26]([OH:28])=[O:27])[C@H:10]([CH:30]2[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 66685270(R)-3-Cyclohexyl-4-(2-methoxycarbonyl-5-phenyl-thiophen-3-yl)-5-oxo-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 66684917HCID 66684917, compoundYield 108.7%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Conditions

Temperature
55 °C

Procedure

To a solution of (R)-3-Cyclohexyl-4-(2-methoxycarbonyl-5-phenyl-thiophen-3-yl)-5-oxo-piperazine-1-carboxylic acid tert-butyl ester (1.8 g, 3.6 mmol) in THF/water/MeOH (1/1/1, 30 mL) was added lithium hydroxide monohydrate (0.45 g, 10.8 mmol, 3.0 equiv) and the resulting solution was heated at 55° C. for 1 hour. The reaction was quenched by addition of 1.0 N HCl aq. solution until pH=5. The solution was then extracted with EtOAc. The organic layer was washed with brine, dried (Na2SO4) and concentrated to give (R)-4-(2-Carboxy-5-phenyl-thiophen-3-yl)-3-cyclohexyl-5-oxo-piperazine-1-carboxylic acid tert-butyl ester 3-((R)-2-Cyclohexyl-6-oxo-piperazin-1-yl)-5-phenyl-thiophene-2-carboxylic acid (1.7 g, 97%). The material was continued to the next step with no further purification.

Workup

  1. customThe reaction was quenched by addition of 1.0 N HCl aq. solution until pH=5
  2. extractionThe solution was then extracted with EtOAc
  3. washThe organic layer was washed with brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-2f1885fc788b45bb8618848267313806
Source dataset
uspto-grants-2015_05
Patent number
US09040690B2

Reaction notes

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