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Lithium Hydroxide → 6-[4-(2-Tert-butoxycarbonylamino-2-dimethylcarbamoyl-ethyl)-phenoxy]-nicotinic acid

HRID 273439
Notes
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Reaction equation

HRID 273439 reaction equation
C[O:2][C:3](=[O:32])[C:4]1[CH:9]=[CH:8][C:7]([O:10][C:11]2[CH:16]=[CH:15][C:14]([CH2:17][CH:18]([NH:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C:19](=[O:23])[N:20]([CH3:22])[CH3:21])=[CH:13][CH:12]=2)=[N:6][CH:5]=1.[OH-].[Li+]>C1COCC1.O>[C:28]([O:27][C:25]([NH:24][CH:18]([C:19](=[O:23])[N:20]([CH3:21])[CH3:22])[CH2:17][C:14]1[CH:15]=[CH:16][C:11]([O:10][C:7]2[CH:8]=[CH:9][C:4]([C:3]([OH:32])=[O:2])=[CH:5][N:6]=2)=[CH:12][CH:13]=1)=[O:26])([CH3:30])([CH3:29])[CH3:31]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 692034916-[4-(2-Tert-butoxycarbonylamino-2-dimethylcarbamoyl-ethyl)-phenoxy]-nicotinic acid methyl ester

Product 1

HCID 691138456-[4-(2-Tert-butoxycarbonylamino-2-dimethylcarbamoyl-ethyl)-phenoxy]-nicotinic acidYield 103.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent
HCID 8028
Tetrahydrofuran
Solvent

Procedure

Amide 18 (1.0 g, 2.25 mmol) was dissolved in THF (10 mL) and diluted with water (10 mL). Lithium hydroxide (0.107 g, 4.5 mmol) was added and the reaction mixture was stirred at room temperature for about 2 h. The THF was evaporated and the resulting aqueous layer was acidified with 2.0 M HCl and extracted into EtOAc (2×100 mL). The organic layer was washed with water (1×100 mL) and brine (1×100 mL), dried and concentrated to yield the desired acid compound 19 (1.0 g, 97%). 1H NMR (400 MHz, DMSO-d6): 13.1 (s, 1H), 8.64 (br, 1H), 8.27 (dd, J=8.4 and 2.0 Hz, 1H), 7.30 (d, J=8.4 Hz, 2H), 7.11 (d, J=8.8 Hz, 1H), 7.08 (m, 3H), 4.56 (m, 1H), 2.94 (s, 3H), 2.85-2.75 (m, 2H), 2.81 (s, 3H), 1.18 (s, 9H).

Workup

  1. customThe THF was evaporated
  2. extractionextracted into EtOAc (2×100 mL)
  3. washThe organic layer was washed with water (1×100 mL) and brine (1×100 mL)
  4. customdried
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-b833ddef85254a78a5c1ba847d211d93
Source dataset
uspto-grants-2008_11
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07456292B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes