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

HRID 1477163Notes

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:37])[C@@H:16]([NH:23][C:24](=[O:36])[C@@H:25]([N:27]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH3:28])[CH3:26])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:5])C.[OH-].[Li+]>C1COCC1.O.CO>[C:32]([O:31][C:29]([N:27]([CH3:28])[C@@H:25]([CH3:26])[C:24]([NH:23][C@@H:16]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[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:37])=[O:36])=[O:30])([CH3:35])([CH3:34])[CH3:33]

Participants

Conditions

Temperature: 23 °C

Procedure

To a solution of (S)-1-{(S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-2-phenyl-acetyl}-2,3-dihydro-1H-indole-2-carboxylic acid ethyl ester (2.28 g, 4.47 mmol, Eq: 1) in 60 mL of THF/water/MeOH (3:1:1) was added 1 M aqueous lithium hydroxide (13.4 mL, 13.4 mmol, Eq: 3). The reaction mixture was stirred at 23° C. for 2.5 h. The reaction was concentrated in vacuo and the residue was taken up in water and acidified with 6 M and then 1 M aqueous HCl to pH˜2. The mixture was extracted with EtOAc (2×50 mL) and the organic layers were combined, dried over Na2SO4 and concentrated in vacuo to afford (S)-1-{(S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-2-phenyl-acetyl}-2,3-dihydro-1H-indole-2-carboxylic acid as a white foam (2.04 g), m/z=482 (M+H).

Workup

concentrationThe reaction was concentrated in vacuo
extractionThe mixture was extracted with EtOAc (2×50 mL)
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-b1faf01a24854738978693d597e2195d
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09403768B2

Reaction notes

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