Benzenepropanoic acid, 4-hydroxy-, methyl ester → HCID 11464914, compound

HRID 855007Notes

Reaction equation

HRID 855007 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1F)[O:8][CH:7]([C:13]([F:16])([F:15])[F:14])[C:6]([C:17]([O:19]CC)=[O:18])=[CH:5]2.[OH:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29][CH2:30][C:31]([O:33]C)=[O:32])=[CH:25][CH:24]=1>>[C:31]([CH2:30][CH2:29][C:26]1[CH:25]=[CH:24][C:23]([O:22][C:11]2[CH:10]=[C:9]3[C:4]([CH:5]=[C:6]([C:17]([OH:19])=[O:18])[CH:7]([C:13]([F:16])([F:14])[F:15])[O:8]3)=[CH:3][C:2]=2[Cl:1])=[CH:28][CH:27]=1)([OH:33])=[O:32]

Participants

3

Reactant 2

HCID 79706Benzenepropanoic acid, 4-hydroxy-, methyl esterHCID 21883602ethyl 6-chloro-7-fluoro-2-(trifluoromethyl)-2H-chromene-3-carboxylate

Product 1

HCID 11464914HCID 11464914, compoundYield 27.6%

Procedure

Using the two step parallel synthesis route from ethyl 6-chloro-7-fluoro-2-(trifluoromethyl)-2H-chromene-3-carboxylate and methyl 3-(4-hydroxyphenyl)propionate, a mixture of two components was obtained. The two products were separated by reverse phase chromatography (C18, 4 cm i.d.×10 cm, 5% to 95% gradient CH3CN/H2O/0.1%TFA). The less retained component (analytical LC retention time=3.40 min, ELS purity >99%) was concd in vacuo to afford 61.1 mg (27.6%) of a white solid: 1H NMR (d6-acetone/400 MHz) 2.59 (t, 2H, J=7.6 Hz), 2.92 (t, 2H, J=7.6 Hz), 5.78 (q, 1H, J=7.1 Hz), 7.04 (d, 2H, J=8.6 Hz), 7.36 (d, 2H, J=8.6 Hz), 7.66 (s, 1H), 7.82 (s, 1H); 19F NMR (d6-acetone/100 MHz) −79.2 (d, 3F, J=6.8 Hz); MS(ES+) 443 (75%, M+1), 465 (100%, M+Na); MS(ES−) 441 (M−1, 100); HRMS (ES−) m/z calcd for (M−1; C20H13O6ClF3) 441.0347, found 441.0347.

Workup

  1. additiona mixture of two components
  2. customwas obtained
  3. customThe two products were separated by reverse phase chromatography (C18, 4 cm i.d.×10 cm, 5% to 95% gradient CH3CN/H2O/0.1%TFA)

Sources & evidence

ORD record
ord-42287e13dcac4c47a8bc50c790d450ab
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Reaction notes

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