Hydrochloric Acid → HCID 24800872, compound

HRID 386463Notes

Reaction equation

HRID 386463 reaction equation
[N:1]1([CH2:6][C:7]2[CH:12]=[CH:11][C:10]([C:13]3[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][C:21]([C:23]4[O:24][C:25]([C:28]5[N:33]=[C:32]([C:34]([O:36]C)=[O:35])[CH:31]=[CH:30][CH:29]=5)=[CH:26][N:27]=4)=[O:22])=[CH:15][CH:14]=3)=[CH:9][CH:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[Li+].[OH-].Cl>C1COCC1.O.C(Cl)Cl>[N:1]1([CH2:6][C:7]2[CH:8]=[CH:9][C:10]([C:13]3[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][C:21]([C:23]4[O:24][C:25]([C:28]5[N:33]=[C:32]([C:34]([OH:36])=[O:35])[CH:31]=[CH:30][CH:29]=5)=[CH:26][N:27]=4)=[O:22])=[CH:15][CH:14]=3)=[CH:11][CH:12]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 24801218HCID 24801218, compound

Product 1

HCID 24800872HCID 24800872, compoundYield 55.9%

Reagents, catalysts & solvents 2

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

Procedure

Methyl 6-(2-(3-(4′-(pyrrolidin-1-ylmethyl)biphenyl-4-yl)propanoyl)oxazol-5-yl)pyridine-2-carboxylate (13 mg, 0.026 mmol) was dissolved in THF/H2O (3:2, 2 mL) and LiOH (1.8 mg, 0.079 mmol) was added. The reaction solution was stirred at room temperature under an atmosphere of Ar for 25 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′-(pyrrolidin-1-ylmethyl)biphenyl-4-yl)propanoyl)oxazol-5-yl)pyridine-2-carboxylic acid as a white solid (7 mg, 55%): 1H NMR (CDCl3, 600 MHz) δ 8.22 (d, 1H, J=6.5 Hz), 8.04-8.02 (m, 3H), 7.67 (d, 2H, J=7.9 Hz), 7.58 (d, 2H, J=7.9 Hz), 7.47 (d, 2H, J=8.1 Hz), 7.33 (d, 2H, J=8.0 Hz), 4.26 (s, 2H), 3.50 (t, 2H, J=7.5 Hz), 3.16 (t, 2H, J=7.5 Hz), 2.45-1.90 (m, 8H); 13C NMR (CDCl3, 150 MHz) δ 187.3, 164.8, 157.5, 151.8, 145.3, 142.3, 140.0, 139.2, 138.0, 131.0, 129.0, 128.6, 128.1, 127.7, 127.2, 124.3, 123.6, 58.0, 52.8, 40.6, 29.4, 23.1; HR ESI-TOF m/z 482.2071 (M+H+, C29H27N3O4, requires 482.2074.

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-aee10dfbe7474a0c9acb4d16bf02dfd3
Source dataset
uspto-grants-2013_02
Patent number
US08372823B2

Reaction notes

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