Lithium hydroxide, monohydrate → (S)-1-((S)-2((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-3-methylbutanoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid

HRID 525294Notes

Reaction equation

HRID 525294 reaction equation
[C:1]([O:5][C:6]([N:8]([CH3:34])[C@@H:9]([CH3:33])[C:10]([NH:12][C@@H:13]([CH:30]([CH3:32])[CH3:31])[C:14]([N:16]1[C:20]2=[N:21][CH:22]=[CH:23][CH:24]=[C:19]2[CH2:18][C@H:17]1[C:25]([O:27]CC)=[O:26])=[O:15])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].O.[OH-].[Li+]>C1COCC1.CO.O>[C:1]([O:5][C:6]([N:8]([CH3:34])[C@@H:9]([CH3:33])[C:10]([NH:12][C@@H:13]([CH:30]([CH3:31])[CH3:32])[C:14]([N:16]1[C:20]2=[N:21][CH:22]=[CH:23][CH:24]=[C:19]2[CH2:18][C@H:17]1[C:25]([OH:27])=[O:26])=[O:15])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 131735253(S)-ethyl 1-((S)-2((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-3-methylbutanoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylate

Product 1

HCID 118353994(S)-1-((S)-2((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-3-methylbutanoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acidYield 100.6%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of (S)-ethyl 1-((S)-2-((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-3-methylbutanoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylate (1.9 g, 3.99 mmol, Eq: 1.00) in THF (36 mL) and MeOH (12 mL) was cooled in an ice bath. To this solution was added a solution of lithium hydroxide monohydrate (0.5 g, 11.9 mmol, Eq: 2.99) in water (12 mL) and the cooling bath was removed. After 1 h, the reaction was quenched by adding 0.1 M aqueous KHSO4 (200 mL) and the mixture was extracted with DCM (2×100 mL). The combined DCM layers were dried over Na2SO4 and concentrated in vacuo. The residue was azeotroped with n-heptane (1×100 mL) to give of (S)-1-((S)-2-((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-3-methylbutanoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid (1.8 g) as a white solid, m/z=449 (M+H).

Workup

  1. customthe cooling bath was removed
  2. customthe reaction was quenched
  3. additionby adding 0.1 M aqueous KHSO4 (200 mL)
  4. extractionthe mixture was extracted with DCM (2×100 mL)
  5. dry with materialThe combined DCM layers were dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was azeotroped with n-heptane (1×100 mL)

Sources & evidence

ORD record
ord-cfd7717b5ce8426da631ede88ccffd77
Source dataset
uspto-grants-2016_05
Patent number
US09340573B2

Reaction notes

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