4-Methoxybenzyl alcohol → 4-Methoxybenzyl 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)picolinate

HRID 1754138Notes

Reaction equation

HRID 1754138 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[F:17])[N:5]=[C:4]([C:18]([OH:20])=[O:19])[C:3]=1[Cl:21].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.[CH3:53][O:54][C:55]1[CH:62]=[CH:61][C:58]([CH2:59]O)=[CH:57][CH:56]=1>C1COCC1>[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[F:17])[N:5]=[C:4]([C:18]([O:20][CH2:59][C:58]2[CH:61]=[CH:62][C:55]([O:54][CH3:53])=[CH:56][CH:57]=2)=[O:19])[C:3]=1[Cl:21]

Participants

6

Reactant 4

HCID 77384-Methoxybenzyl alcoholHCID 11776Triphenylphosphine2×HCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 25181547Halauxifen

Product 1

HCID 704975304-Methoxybenzyl 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)picolinateYield 26%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)picolinic acid (600 mg, 1.81 mmol) in THF (10 mL) was added triphenylphosphine (475 mg, 1.81 mmol), diethyl azodicarboxylate (0.29 mL, 1.81 mmol), and 4-methoxybenzyl alcohol (0.34 mL, 2.72 mmol). The reaction mixture was stirred for 48 h. Additional triphenylphosphine (475 mg, 1.81 mmol) was added to the reaction, and the reaction mixture was stirred for 24 h. The reaction mixture was concentrated to dryness and was purified by silica gel chromatography (eluting with a 0-100% EtOAc/hexane gradient) to provide an off-white solid (170 mg, 26%): mp 73-83° C.; 1H NMR (400 MHz, CDCl3) δ 7.66 (dd, J=8.6, 7.8 Hz, 1H), 7.45-7.38 (m, 2H), 7.22 (dd, J=8.7, 1.8 Hz, 1H), 7.16 (d, J=1.7 Hz, 1H), 6.94-6.87 (m, 2H), 5.38 (s, 2H), 4.80 (s, 2H), 3.96 (d, J=0.8 Hz, 3H), 3.81 (s, 3H); ESIMS m/z 451 ([M+H]+), 449 ([M−H]−).

Workup

  1. stirringthe reaction mixture was stirred for 24 h
  2. concentrationThe reaction mixture was concentrated to dryness
  3. customwas purified by silica gel chromatography (
  4. washeluting with a 0-100% EtOAc/hexane gradient)

Sources & evidence

ORD record
ord-9b5f2f5ef23e4a228cfd585cd51af54c
Source dataset
uspto-grants-2015_10
Patent number
US09169217B2

Reaction notes

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