Hydrochloric Acid → HCID 24801220, compound

HRID 386460Notes

Reaction equation

HRID 386460 reaction equation
[N:1]1([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][C:22]([C:24]4[O:25][C:26]([C:29]5[N:34]=[C:33]([C:35]([O:37]C)=[O:36])[CH:32]=[CH:31][CH:30]=5)=[CH:27][N:28]=4)=[O:23])=[CH:16][CH:15]=3)=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Li+].[OH-].Cl>C1COCC1.O.C(Cl)Cl>[N:1]1([CH2:7][C:8]2[CH:9]=[CH:10][C:11]([C:14]3[CH:15]=[CH:16][C:17]([CH2:20][CH2:21][C:22]([C:24]4[O:25][C:26]([C:29]5[N:34]=[C:33]([C:35]([OH:37])=[O:36])[CH:32]=[CH:31][CH:30]=5)=[CH:27][N:28]=4)=[O:23])=[CH:18][CH:19]=3)=[CH:12][CH:13]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 24800868HCID 24800868, compound

Product 1

HCID 24801220HCID 24801220, compoundYield 38%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21881883Oxolane--water (1/1)Solvent

Procedure

Methyl 6-(2-(3-(4′-(piperidin-1-ylmethyl)biphenyl-4-yl)propanoyl)oxazol-5-yl)pyridine-2-carboxylate (11 mg, 0.022 mmol) was dissolved in THF/H2O (3:2, 2 mL) and LiOH (1.5 mg, 0.065 mmol) was added. The reaction solution was stirred at room temperature under an atmosphere of Ar for 20 min before the addition of aqueous 1 N HCl to pH 4. The reaction solution was diluted with CH2Cl2 and the organic and aqueous layers were separated. The aqueous layer was made basic to pH 8 with the addition of saturated aqueous NaHCO3 and extracted with CH2Cl2. The organic phases were combined, dried over Na2SO4, and concentrated in vacuo. The crude product was purified by tritration in ether to provide 6-(2-(3-(4′-(piperidin-1-ylmethyl)biphenyl-4-yl)propanoyl)oxazol-5-yl)pyridine-2-carboxylic acid as a white solid (4 mg, 38%): 1H NMR (CDCl3, 600 MHz) δ 8.22 (d, 1H, J=5.7 Hz), 8.05-8.01 (m, 3H), 7.63 (d, 2H, J=8.0 Hz), 7.58 (d, 2H, J=8.0 Hz), 7.47 (d, 2H, J=8.0 Hz), 7.33 (d, 2H, J=8.0 Hz), 4.20 (s, 2H), 3.50 (t, 21-1, J=7.5 Hz), 3.15 (t, 2H, J=7.4 Hz), 2.15-1.95 (m, 10H); 13C NMR (CDCl3, 150 MHz) δ 187.2, 165.8, 157.4, 152.1, 145.4, 142.4, 140.1, 138.9, 138.0, 131.9, 129.0, 128.0, 127.6, 127.3, 127.2, 124.4, 123.2, 60.5, 52.6, 40.5, 29.4, 22.6, 22.2; HR ESI-TOF m/z 496.2227 (M+H+, C30H29N3O4, requires 496.2231).

Workup

  1. customthe organic and aqueous layers were separated
  2. additionThe aqueous layer was made basic to pH 8 with the addition of saturated aqueous NaHCO3
  3. extractionextracted with CH2Cl2
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by tritration in ether

Sources & evidence

ORD record
ord-e15d88d682d4442a837340a88afbd4fe
Source dataset
uspto-grants-2013_02
Patent number
US08372823B2

Reaction notes

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