Lithium Hydroxide → 3-{4-[4-(2-Tert-butoxycarbonylamino-3-morpholin-4-yl-3-oxopropyl)-phenoxy]-phenyl}-propionic acid

HRID 748986Notes

Reaction equation

HRID 748986 reaction equation
C[O:2][C:3](=[O:37])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]2[CH:18]=[CH:17][C:16]([CH2:19][CH:20]([NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C:21]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)=[O:22])=[CH:15][CH:14]=2)=[CH:8][CH:7]=1.[OH-].[Li+]>C1COCC1.O>[C:33]([O:32][C:30]([NH:29][CH:20]([C:21]([N:23]1[CH2:24][CH2:25][O:26][CH2:27][CH2:28]1)=[O:22])[CH2:19][C:16]1[CH:15]=[CH:14][C:13]([O:12][C:9]2[CH:10]=[CH:11][C:6]([CH2:5][CH2:4][C:3]([OH:37])=[O:2])=[CH:7][CH:8]=2)=[CH:18][CH:17]=1)=[O:31])([CH3:36])([CH3:34])[CH3:35]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 597628203-{4-[4-(2-Tert-butoxycarbonylamino-3-morpholin-4-yl-3-oxo-propyl)-phenoxy]-phenyl}-propionic acid methyl ester

Product 1

HCID 597628083-{4-[4-(2-Tert-butoxycarbonylamino-3-morpholin-4-yl-3-oxopropyl)-phenoxy]-phenyl}-propionic acidYield 93.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

The amide 13 (2.2 g, 4.3 mmol) was dissolved in THF (25 mL) and diluted with water (25 mL). Lithium hydroxide (0.41 g, 17.0 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 (2×50 mL). The organic layer was washed with water (1×50 mL) and brine (1×50 mL), dried and concentrated to yield the desired acid compound 14 (2.0 g, 93.5%). 1H NMR (400 MHz, DMSO-d6): 12.1 (br, 1H), 7.20 (d, J=8.4 Hz, 2H), 7.17 (d, J=8.8 Hz, 2H), 7.14 (d, J=8.4 Hz, 1H), 6.86 (d, J=8.4 Hz, 2H), 6.82 (d, J=8.8 Hz, 2H), 4.52 (m, 1H), 3.22-3.47 (m, 8H), 2.72-2.80 (m, 4H), 1.28 (s, 9H).

Workup

  1. customThe THF was evaporated
  2. extractionextracted into EtOAc (2×50 mL)
  3. washThe organic layer was washed with water (1×50 mL) and brine (1×50 mL)
  4. customdried
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-93ed2454973c4893b09a3f6013b4b655
Source dataset
uspto-grants-2008_07
Patent number
US07399786B2

Reaction notes

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