Hydrochloric Acid → 1-(2-{2-Ethyl-4-[5-(5-isobutyl-4-methyl-pyridin-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-ethyl)-azetidine-3-carboxylic acid

HRID 2037372Notes

Reaction equation

HRID 2037372 reaction equation
[CH2:1]([C:3]1[CH:16]=[C:15]([C:17]2[N:21]=[C:20]([C:22]3[CH:27]=[C:26]([CH3:28])[C:25]([CH2:29][CH:30]([CH3:32])[CH3:31])=[CH:24][N:23]=3)[O:19][N:18]=2)[CH:14]=[C:13]([CH3:33])[C:4]=1[O:5][CH2:6][CH2:7]OS(C)(=O)=O)[CH3:2].C[O:35][C:36]([CH:38]1[CH2:41][NH:40][CH2:39]1)=[O:37].C(N(CC)CC)C.Cl>C(O)C.[OH-].[Na+]>[CH2:1]([C:3]1[CH:16]=[C:15]([C:17]2[N:21]=[C:20]([C:22]3[CH:27]=[C:26]([CH3:28])[C:25]([CH2:29][CH:30]([CH3:31])[CH3:32])=[CH:24][N:23]=3)[O:19][N:18]=2)[CH:14]=[C:13]([CH3:33])[C:4]=1[O:5][CH2:6][CH2:7][N:40]1[CH2:41][CH:38]([C:36]([OH:35])=[O:37])[CH2:39]1)[CH3:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 20132751Methyl azetidine-3-carboxylateHCID 86649451Methanesulfonic acid 2-{2-ethyl-4-[5-(5-isobutyl-4-methyl-pyridin-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-ethyl ester

Product 1

HCID 686287941-(2-{2-Ethyl-4-[5-(5-isobutyl-4-methyl-pyridin-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-ethyl)-azetidine-3-carboxylic acidYield 19,305.199%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 14798Sodium HydroxideSolvent

Procedure

A solution of methanesulfonic acid 2-{2-ethyl-4-[5-(5-isobutyl-4-methyl-pyridin-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-ethyl ester (300 mg, 633 μmol), azetidine-3-carboxylic acid methyl ester (218 mg, 1.84 μmol) and triethylamine (129 mg, 1.26 mmol) in ethanol (10 mL) is stirred in a sealed vial at 80° C. for 96 h. The mixture is cooled to rt, diluted with 3 M aq. NaOH and again stirred at rt for 1 h. The mixture is acidified by adding aq. HCl and is then extracted with EA (2×25 mL). The org. extracts are combined, dried over MgSO4, filtered and concentrated. The crude product is purified by prep. HPLC to give the title compound (170 mg) as a colourless oil; LC-MS: tR=0.90 min, [M+H]+=479.10; 1H NMR (CDCl3): δ0.98 (d, J=6.5 Hz, 6H), 1.282 (t, J=7.0 Hz, 3H), 1.93 (hept, J=7.0 Hz, 1H), 2.38 (s, 3H), 2.45 (s, 3H), 2.61 (d, J=7.3 Hz, 2H), 2.73 (q, J=7.3 Hz, 2H), 3.71-3.82 (m, 2H), 3.97-4.08 (m, 1H), 4.19-4.27 (m, 2H), 4.37-4.62 (m, 2H), 4.73-4.97 (m, 2H), 7.87 (s, 1H), 7.89 (s, 1H), 8.07 (s, 1H), 8.53 (s, 1H).

Workup

  1. extractionis then extracted with EA (2×25 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product is purified by prep

Sources & evidence

ORD record
ord-e6f9133cbc614d42a0bb3c732378259a
Source dataset
uspto-grants-2013_11
Patent number
US08575200B2

Reaction notes

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