Methanol → HCID 66585022, compound

HRID 1629998Notes

Reaction equation

HRID 1629998 reaction equation
[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:10][C:5]2=[C:4]([C:18]([O:20]C)=[O:19])[C:3]=1[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]#[N:29])[CH:23]=1.CO.[OH-].[Li+].S(=O)(=O)(O)O>ClCCl.O.O1CCCC1>[C:14]([O:13][C:11]([N:9]1[CH2:8][CH2:7][N:6]2[C:2]([Cl:1])=[C:3]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([C:28]#[N:29])[CH:23]=3)[C:4]([C:18]([OH:20])=[O:19])=[C:5]2[CH2:10]1)=[O:12])([CH3:17])([CH3:15])[CH3:16]

Participants

8

Reactant 4

HCID 887MethanolHCID 1118Sulfuric AcidHCID 3939Lithium HydroxideHCID 66585001HCID 66585001, compound

Product 1

HCID 66585022HCID 66585022, compoundYield 63.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a suspension of 5.50 g (13.2 mmol) of 2-tert-butyl 8-methyl 6-chloro-7-(3-cyanophenyl)-3,4-dihydropyrrolo[1,2-a]pyrazine-2,8(1H)-dicarboxylate in 60 ml of a mixture of methanol, water and tetrahydrofuran (1:1:2) is added 0.38 g (15.9 mmol) of lithium hydroxide, and the mixture is heated at 60° C. for 18 hours. The mixture is then taken up in 100 ml of dichloromethane and 100 ml of water, and is then acidified by addition of aqueous 1N sulfuric acid. The organic phase is separated out and dried over sodium sulfate, and the solvent is evaporated off under reduced pressure to give a yellow solid, which is purified by chromatography on a column of 80 g of silica gel, eluting with a mixture of 2% methanol in dichloromethane, to give 3.35 g of 2-(tert-butyloxycarbonyl)-6-chloro-7-(3-cyanophenyl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxylic acid in the form of a white powder after triturating in acetonitrile, filtering off and drying.

Workup

  1. customThe organic phase is separated out
  2. dry with materialdried over sodium sulfate
  3. customthe solvent is evaporated off under reduced pressure
  4. customto give a yellow solid, which
  5. customis purified by chromatography on a column of 80 g of silica gel
  6. washeluting with a mixture of 2% methanol in dichloromethane

Sources & evidence

ORD record
ord-e7ad304d843441b49bfd14ffee331918
Source dataset
uspto-grants-2014_07
Patent number
US08791119B2

Reaction notes

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