HCID 57507746, compound → HCID 70497874, compound

HRID 333648Notes

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-f4fa09ad55904809817a0e5a79e1b81c
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08883688B2

Reaction notes

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