2-(Methoxymethyl)-2'-methylbiphenyl-4-carboxylic acid → Tert-butyl (2-fluoro-4-{5-[2-(methoxymethyl)-2'-methylbiphenyl-4-yl]-1,2,4-oxadiazol-3-yl}phenoxy)acetate

HRID 219988Notes

Reaction equation

HRID 219988 reaction equation
[CH3:1][O:2][CH2:3][C:4]1[CH:9]=[C:8]([C:10]([OH:12])=O)[CH:7]=[CH:6][C:5]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH3:19].[NH2:20][C:21](=[N:38]O)[C:22]1[CH:36]=[CH:35][C:25]([O:26][CH2:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])=[C:24]([F:37])[CH:23]=1>>[F:37][C:24]1[CH:23]=[C:22]([C:21]2[N:20]=[C:10]([C:8]3[CH:7]=[CH:6][C:5]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=4[CH3:19])=[C:4]([CH2:3][O:2][CH3:1])[CH:9]=3)[O:12][N:38]=2)[CH:36]=[CH:35][C:25]=1[O:26][CH2:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29]

Participants

3

Reactant 2

HCID 594958222-(Methoxymethyl)-2'-methylbiphenyl-4-carboxylic acidHCID 72307490Tert-butyl {4-[amino(hydroxyimino)methyl]-2-fluorophenoxy}acetate

Product 1

HCID 86645660Tert-butyl (2-fluoro-4-{5-[2-(methoxymethyl)-2'-methylbiphenyl-4-yl]-1,2,4-oxadiazol-3-yl}phenoxy)acetate

Procedure

The title compound was prepared following procedure described for example 4, step 1, but starting from Intermediate 28 (1 281.50 mg; 5 mmol) and Intermediate 49 (1 421.44 mg; 5 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 white powder. 1H NMR (CDCl3) δ 8.41 (d, J=1.3 Hz, 1H), 8.15 (dd, J=7.8, 1.8 Hz, 1H), 7.98-7.91 (m, 2H), 7.36-7.23 (m, 4H), 7.13 (d, J=7.1 Hz, 1H), 7.03-6.97 (m, 1H), 4.68 (s, 2H), 4.22 (s, 2H), 3.33 (s, 3H), 2.07 (s, 3H), 1.49 (s, 9H). LC/MS (Method B): 505.2 (M+H)+. HPLC (Method A) Rt 6.36 min (Purity: 98.6%).

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-d9b3126bb9ad47b99de22134b5420ab1
Source dataset
uspto-grants-2012_06
Patent number
US08202865B2

Reaction notes

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