2'-Ethyl-2-(methoxymethyl)-[1,1'-biphenyl]-4-carboxylic acid → Ethyl 4-(4-{5-[2'-ethyl-2-(methoxymethyl)biphenyl-4-yl]-1,2,4-oxadiazol-3-yl}-2-fluorophenoxy)butanoate

HRID 219985Notes

Reaction equation

HRID 219985 reaction equation
[CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:14]=[CH:13][C:12]([C:15](O)=O)=[CH:11][C:10]=1[CH2:18][O:19][CH3:20])[CH3:2].[NH2:21][C:22](=[N:39][OH:40])[C:23]1[CH:37]=[CH:36][C:26]([O:27][CH2:28][CH2:29][CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])=[C:25]([F:38])[CH:24]=1>>[CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:14]=[CH:13][C:12]([C:15]2[O:40][N:39]=[C:22]([C:23]3[CH:37]=[CH:36][C:26]([O:27][CH2:28][CH2:29][CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])=[C:25]([F:38])[CH:24]=3)[N:21]=2)=[CH:11][C:10]=1[CH2:18][O:19][CH3:20])[CH3:2]

Participants

3

Reactant 2

HCID 594958092'-Ethyl-2-(methoxymethyl)-[1,1'-biphenyl]-4-carboxylic acidHCID 72307473Ethyl 4-{4-[amino(hydroxyimino)methyl]-2-fluorophenoxy}butanoate

Product 1

HCID 67528056Ethyl 4-(4-{5-[2'-ethyl-2-(methoxymethyl)biphenyl-4-yl]-1,2,4-oxadiazol-3-yl}-2-fluorophenoxy)butanoate

Procedure

The title compound was prepared following procedure described for example 4, step 1, but starting from Intermediate 36 (202.74 mg; 0.75 mmol) and Intermediate 66 (234.54 mg; 0.83 mmol). The reaction mixture was filtered through a SPE NH2 column (10 g) and rinsed with ACN. The filtrate was passed through a SPE SCX column (10 g) and rinsed with ACN. After evaporation of the solvents, the crude product was purified by flash chromatography (c-hex/(DCM/EtOAc 1:1) gradient from 1:0 to 1:1), affording the title compound as a colorless oil. 1H NMR (CDCl3) δ 8.41 (d, J=1.3 Hz, 1H), 8.15 (dd, J=7.9, 1.8 Hz, 1H), 7.95-7.90 (m, 2H), 7.41-7.34 (m, 3H), 7.29-7.23 (m, 1H), 7.12-7.05 (m, 2H), 4.22-4.13 (m, 6H), 3.33 (s, 3H), 2.57 (t, J=7.2 Hz, 2H), 2.50-2.28 (m, 2H), 2.24-2.17 (m, 2H), 1.27 (t, J=7.2 Hz, 3H), 1.05 (t, J=7.5 Hz, 3H). LC/MS (Method B): 519.4 (M+H)+. HPLC (Method A) Rt 6.62 min (Purity: 99.9%).

Workup

  1. customThe title compound was prepared following procedure
  2. filtrationThe reaction mixture was filtered through a SPE NH2 column (10 g)
  3. washrinsed with ACN
  4. washrinsed with ACN
  5. customAfter evaporation of the solvents
  6. customthe crude product was purified by flash chromatography (c-hex/(DCM/EtOAc 1:1) gradient from 1:0 to 1:1)

Sources & evidence

ORD record
ord-34fc034bd8354dcf9f964c6716e64744
Source dataset
uspto-grants-2012_06
Patent number
US08202865B2

Reaction notes

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