Lithium Hydroxide → (S)-1-{(S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-3-methyl-butyryl}-2,3-dihydro-1H-indole-2-carboxylic acid

HRID 1477158Notes

Reaction equation

C([O:3][C:4]([C@@H:6]1[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[N:7]1[C:15](=[O:34])[C@@H:16]([NH:20][C:21](=[O:33])[C@@H:22]([N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH3:25])[CH3:23])[CH:17]([CH3:19])[CH3:18])=[O:5])C.[OH-].[Li+]>C1COCC1.O.CO>[C:29]([O:28][C:26]([N:24]([CH3:25])[C@@H:22]([CH3:23])[C:21]([NH:20][C@@H:16]([CH:17]([CH3:18])[CH3:19])[C:15]([N:7]1[C:8]2[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:14][C@H:6]1[C:4]([OH:5])=[O:3])=[O:34])=[O:33])=[O:27])([CH3:32])([CH3:31])[CH3:30]

Participants

Conditions

Temperature: 23 °C

Procedure

To a solution of (S)-1-{(S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-3-methyl-butyryl}-2,3-dihydro-1H-indole-2-carboxylic acid ethyl ester (2.93 g, 6.16 mmol) in THF/water/methanol (3:1:1; 60 mL) was added 1 M aqueous lithium hydroxide (18.5 mL, 18.5 mmol). The reaction mixture was stirred at 23° C. for 2.5 h and then concentrated in vacuo. The residue was diluted with water and acidified with 6 M and then 1 M aqueous HCl to pH˜2. The mixture was extracted with EtOAc, the organic layer was dried over Na2SO4 and concentrated in vacuo to give (S)-1-{(S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-3-methyl-butyryl}-2,3-dihydro-1H-indole-2-carboxylic acid (2.70 g) as an off-white foam, m/z=470 (M+Na).

Workup

concentrationconcentrated in vacuo
additionThe residue was diluted with water
extractionThe mixture was extracted with EtOAc
dry with materialthe organic layer was dried over Na2SO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-972d262fd7804f75a0d015842f5aef75
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09403768B2

Reaction notes

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