Lithium hydroxide, monohydrate → (S)-1-((S)-2-(tert-butoxycarbonylamino)-3-methylbutanoyl)indoline-2-carboxylic acid

HRID 1477167Notes

Reaction equation

HRID 1477167 reaction equation
O.[OH-].[Li+].[C:4]([O:8][C:9]([NH:11][C@@H:12]([CH:29]([CH3:31])[CH3:30])[C:13]([N:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:17][C@H:16]1[C:24]([O:26]CC)=[O:25])=[O:14])=[O:10])([CH3:7])([CH3:6])[CH3:5]>O.C1COCC1.CO>[C:4]([O:8][C:9]([NH:11][C@@H:12]([CH:29]([CH3:31])[CH3:30])[C:13]([N:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:17][C@H:16]1[C:24]([OH:26])=[O:25])=[O:14])=[O:10])([CH3:7])([CH3:6])[CH3:5]

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 107154341H-Indole-2-carboxylic acid, 1-[2-[[(1,1-dimethylethoxy)carbonyl]amino]-3-methyl-1-oxobutyl]-2,3-dihydro-, ethyl ester, [S-(R*,R*)]-

Product 1

HCID 10618657(S)-1-((S)-2-(tert-butoxycarbonylamino)-3-methylbutanoyl)indoline-2-carboxylic acidYield 103.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Lithium hydroxide monohydrate (187 mg, 4.46 mmol, Eq: 3) in water (4.5 mL) was added to an ice-bath cooled solution of (S)-ethyl 1-((S)-2-(tert-butoxycarbonylamino)-3-methylbutanoyl)indoline-2-carboxylate (0.58 g, 1.49 mmol, Eq: 1.00) in THF (13.5 mL) and MeOH (4.5 mL). The cooling bath was removed and the reaction was stirred at rt for 1 h. 0.1 M Aqueous KHSO4 (50 mL) was added to the reaction mixture and the resulting mixture was extracted with DCM (2×50 mL). The aqueous layer was further acidified with 1 M aqueous HCl (˜5 mL) and extracted again with DCM (2×50 mL). The organic layers were combined, dried over Na2SO4 and concentrated in vacuo. The residue was azeotroped with hexanes to give (S)-1-((S)-2-(tert-butoxycarbonylamino)-3-methylbutanoyl)indoline-2-carboxylic acid (0.56 g), m/z=363 (M+H).

Workup

  1. customThe cooling bath was removed
  2. addition0.1 M Aqueous KHSO4 (50 mL) was added to the reaction mixture
  3. extractionthe resulting mixture was extracted with DCM (2×50 mL)
  4. extractionextracted again with DCM (2×50 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was azeotroped with hexanes

Sources & evidence

ORD record
ord-974bfb805e1246178784cd916f97e6fd
Source dataset
uspto-grants-2016_08
Patent number
US09403768B2

Reaction notes

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