HCID 72942111, compound → HCID 72217216, compound

HRID 1161880Notes

Reaction equation

HRID 1161880 reaction equation
[C:1]([O:5][C:6](=[O:19])[CH2:7][C:8]1[C:13]([C:14]([F:17])([F:16])[F:15])=[CH:12][CH:11]=[C:10]([Cl:18])[N:9]=1)(C)(C)[CH3:2].C(OC(=O)CC1C=CC(C(F)(F)F)=C(Cl)N=1)(C)(C)C>CCO.Cl.CCOC(C)=O>[CH2:1]([O:5][C:6](=[O:19])[CH2:7][C:8]1[C:13]([C:14]([F:17])([F:15])[F:16])=[CH:12][CH:11]=[C:10]([Cl:18])[N:9]=1)[CH3:2]

Participants

6

Reactant 2

HCID 72942111HCID 72942111, compoundHCID 86603872HCID 86603872, compound

Product 1

HCID 72217216HCID 72217216, compound

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A 1:2.5 mixture of (6-chloro-3-trifluoromethyl-pyridin-2-yl)-acetic acid tert-butyl ester and (6-chloro-5-trifluoromethyl-pyridin-2-yl)-acetic acid tert-butyl ester (semi-crude; 10.15 g, 34.33 mmol) is dissolved in EtOH (100 ml) previously saturated at 0° C. with HCl gas. The solution is heated to 90° C. After 30 minutes at 90° C., TLC analysis indicates full conversion of the starting material. The solvent is completely evaporated. The crude reaction product is dissolved in EtOAc, washed once with conc. aqueous NaHCO3 and once with H2O (backextracted with EtOAc). The organic layer is dried over Na2SO4 and concentrated. Careful purification by FCC (hexanes/EtOAc 100:0, 97:3, 95:5, 9:1, 85:15, 8:2 to 7:3) separates the two regioisomeric compounds, (6-chloro-3-trifluoromethyl-pyridin-2-yl)-acetic acid tert-butyl ester and (6-chloro-5-trifluoromethyl-pyridin-2-yl)-acetic acid ethyl ester. Analytical data for (6-Chloro-3-trifluoromethyl-pyridin-2-yl)-acetic acid ethyl ester: 1H NMR (CDCl3, 400 MHz) δ 1.28 (t, J=6.7 Hz, 3H), 3.95 (s, 2H), 4.12 (q, J=6.7 Hz, 2H), 7.32 (d, J=8.9 Hz, 1H), 7.85 (d, J=8.9 Hz, 1H); ES-MS: 268.2 [M+H]+.

Workup

  1. customThe solvent is completely evaporated
  2. customThe crude reaction product
  3. washwashed once with conc. aqueous NaHCO3 and once with H2O (backextracted with EtOAc)
  4. dry with materialThe organic layer is dried over Na2SO4
  5. concentrationconcentrated
  6. customCareful purification by FCC (hexanes/EtOAc 100:0, 97:3, 95:5, 9:1, 85:15, 8:2 to 7:3)

Sources & evidence

ORD record
ord-3159f74892f44c1d9c92e99129ea638c
Source dataset
uspto-grants-2010_10
Patent number
US07820672B2

Reaction notes

Loading…