Trifluoroacetic acid → 4-(2-Chloro-4-(5-(2-cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-6-methylphenoxy)butanoic acid

HRID 2278799Notes

Reaction equation

HRID 2278799 reaction equation
[Cl:1][C:2]1[CH:18]=[C:17]([C:19]2[N:23]=[C:22]([C:24]3[CH:29]=[C:28]([O:30][CH3:31])[N:27]=[C:26]([CH:32]4[CH2:36][CH2:35][CH2:34][CH2:33]4)[CH:25]=3)[O:21][N:20]=2)[CH:16]=[C:15]([CH3:37])[C:3]=1[O:4][CH2:5][CH2:6][CH2:7][C:8]([O:10]C(C)(C)C)=[O:9].C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:18]=[C:17]([C:19]2[N:23]=[C:22]([C:24]3[CH:29]=[C:28]([O:30][CH3:31])[N:27]=[C:26]([CH:32]4[CH2:33][CH2:34][CH2:35][CH2:36]4)[CH:25]=3)[O:21][N:20]=2)[CH:16]=[C:15]([CH3:37])[C:3]=1[O:4][CH2:5][CH2:6][CH2:7][C:8]([OH:10])=[O:9]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 70559037Tert-butyl 4-(2-chloro-4-(5-(2-cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-6-methylphenoxy)butanoate

Product 1

HCID 575249404-(2-Chloro-4-(5-(2-cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-6-methylphenoxy)butanoic acidYield 73.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of tert-butyl 4-(2-chloro-4-(5-(2-cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-6-methylphenoxy)butanoate (90 mg, 170 μmol) in DCM (5 mL) is cooled to 0° C. before TFA (1 mL) is added. The mixture is stirred at 0° C. for 10 min, then at rt for 30 min. The mixture is again cooled to 0° C. before another portion of TFA (1 mL) is added. Stirring is continued at rt for 2 h. The mixture is concentrated and the crude product is purified by prep. HPLC to give the title compound (59 mg) as white solid; LC-MS: tR=1.14 min, [M+H]+=472.29; 1H NMR (CDCl3): δ 8.13 (s br, 1H), 8.02 (d, J=1.4 Hz, 1H), 7.88 (d, J=0.7 Hz, 1H), 7.47 (s, 1H), 7.25 (s, 1H), 4.05 (t, J=5.9 Hz, 2H), 4.00 (s, 3H), 3.17-3.28 (m, 1H), 2.74 (t, J=7.3 Hz, 2H), 2.39 (s, 3H), 2.21 (quint, J=6.5 Hz, 2H), 2.05-2.15 (m, 2H), 1.81-1.95 (m, 4H), 1.68-1.80 (m, 2H).

Workup

  1. additionis added
  2. waitat rt for 30 min
  3. additionis added
  4. stirringStirring
  5. waitis continued at rt for 2 h
  6. concentrationThe mixture is concentrated
  7. customthe crude product is purified by prep

Sources & evidence

ORD record
ord-2320f39ad51a4602984a58e6616a954f
Source dataset
uspto-grants-2015_09
Patent number
US09133179B2

Reaction notes

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