Hydrochloric Acid → HCID 24800871, compound

HRID 386462Notes

Reaction equation

HRID 386462 reaction equation
[S:1]1[CH2:6][CH2:5][N:4]([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)[CH2:3][CH2:2]1.[Li+].[OH-].Cl>C1COCC1.O.C(Cl)Cl>[S:1]1[CH2:6][CH2:5][N:4]([CH2:7][C:8]2[CH:9]=[CH:10][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]([OH:37])=[O:36])[CH:32]=[CH:31][CH:30]=5)=[CH:27][N:28]=4)=[O:23])=[CH:16][CH:15]=3)=[CH:12][CH:13]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 24801217HCID 24801217, compound

Product 1

HCID 24800871HCID 24800871, compoundYield 87.1%

Reagents, catalysts & solvents 2

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

Procedure

Methyl 6-(2-(3-(4′-(thiomorpholinomethyl)biphenyl-4-yl)propanoyl)oxazol-5-yl)pyridine-2-carboxylate (105 mg, 0.199 mmol) was dissolved in THF/H2O (3:2, 15 mL) and LiOH (14 mg, 0.60 mmol) was added. The reaction solution was stirred at room temperature under an atmosphere of Ar for 40 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′-(thiomorpholinomethyl)biphenyl-4-yl)propanoyl)oxazol-5-yl)pyridine-2-carboxylic acid (89 mg, 87%): 1H NMR (CDCl3, 600 MHz) δ 8.21 (d, 1H, J=6.9 Hz), 8.05-8.00 (m, 3H), 7.52 (d, 2H, J=8.1 Hz), 7.49 (d, 2H, J=8.1 Hz), 7.40 (d, 2H, J=8.0 Hz), 7.32 (d, 2H, J=8.0 Hz), 3.83 (s, 2H), 3.50 (t, 2H, J=7.5 Hz), 3.15 (t, 2H, J=7.5 Hz), 2.99 (s, 4H), 2.83-2.82 (m, 4H); 13C NMR (CDCl3, 150 MHz) δ 187.3, 157.4, 152.2, 149.6, 145.5, 140.7, 139.6, 138.9, 138.6, 130.4, 128.9, 128.0, 127.2, 127.1, 124.5, 123.2, 62.4, 54.2, 40.6, 29.3, 26.9; HR ESI-TOF m/z 514.1784 (M+H+, C29H27N3O4S, requires 514.1795).

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-aba5b1d9b60747c2abf628cc7a89566c
Source dataset
uspto-grants-2013_02
Patent number
US08372823B2

Reaction notes

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