HCID 57507746, compound → HCID 70497874, compound

HRID 1754139Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[C:10]([O:15][CH3:16])[C:9]=2[Cl:17])[N:5]=[C:4]([C:18]([O:20][CH3:21])=[O:19])[C:3]=1[Cl:22]>C(O)C1C=CC=CC=1.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[NH2:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[C:10]([O:15][CH3:16])[C:9]=2[Cl:17])[N:5]=[C:4]([C:18]([O:20][CH2:21][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[O:19])[C:3]=1[Cl:22]

Participants

Conditions

Temperature: 87.5 °C

Procedure

Methyl 4-amino-3-chloro-6-(2,4-dichloro-3-methoxyphenyl)picolinate (Compound C, prepared by the methods described in U.S. Pat. No. 7,314,849 B2; 500 mg, 1.4 mmol) was dissolved in benzyl alcohol (10 mL), treated with titanium(IV) isopropoxide (ca 100 μL) and heated at 85-90° C. After 2 h, another portion of titanium(IV) isopropoxide (100 μL) was added and heating was continued for another 18 h. The volatiles were removed under high vacuum, and the residue was purified by silica gel chromatography (eluting with 5% Et2O-30% dichloromethane (CH2Cl2)-65% hexane). The material was further purified by reverse phase high performance liquid chromatography (RP-HPLC; eluting with 70% acetonitrile) to give the title compound (375 mg, 61%): mp 107-108° C.; 1H NMR (400 MHz, CDCl3) δ 7.50-7.26 (m, 8H), 6.97 (s, 1H), 5.42 (s, 2H), 4.85 (s, 2H), 3.91 (s, 3H); ESIMS m/z 437 ([M+H]+).

Workup

temperatureheating
waitwas continued for another 18 h
customThe volatiles were removed under high vacuum
customthe residue was purified by silica gel chromatography (eluting with 5% Et2O-30% dichloromethane (CH2Cl2)-65% hexane)
customThe material was further purified by reverse phase high performance liquid chromatography (RP-HPLC; eluting with 70% acetonitrile)

Sources & evidence

ORD record: ord-8f99df0274ef46c38264a0be96fedd4b
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09169217B2

Reaction notes

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