Hydrochloric Acid → (E)-3-(6-(3-tert-butoxy-3-oxoprop-1-enyl)-5-fluoropyridin-2-yl)-2-(tert-butoxycarbonylamino)propanoic acid

HRID 1524853Notes

Reaction equation

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

Participants

Conditions

Temperature: 0 °C

Procedure

3-(6-(3-tert-Butoxy-3-oxopropyl)-5-fluoropyridin-2-yl)-2-(tert-butoxycarbonylamino)propanoic acid. To a solution of 139C (0.68 g, 1.551 mmol) in THF (10 mL) and water (3 mL) was added LiOH (0.074 g, 3.10 mmol) at 0° C. The reaction was stirred under argon at 0° C. for 2 hrs. 1.0 N HCl (3.1 mL) was added to neutralize the reaction. The reaction mixture was diluted with EtOAc, washed with H2O and brine. The organic phase was dried over magnesium sulfate, filtered and concentrated to give a tan solid of (E)-3-(6-(3-tert-butoxy-3-oxoprop-1-enyl)-5-fluoropyridin-2-yl)-2-(tert-butoxycarbonylamino)propanoic acid. MS (ESI) m/z: 411.1 (M+H)+. To the above obtained intermediate were added catalytic amount of 10% Pd/C and MeOH (15 mL). The reaction mixture was stirred under a hydrogen balloon at rt for 1 h. Catalyst was filtered off and solvent was removed to give 139D as a tan solid. MS (ESI) m/z: 413.1 (M+H)+.

Workup

customthe reaction
washwashed with H2O and brine
dry with materialThe organic phase was dried over magnesium sulfate
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-abb45e6bbe44440f8c6e8a2e4321e461
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09079918B2

Reaction notes

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