Pyridine → Methyl 2-nitro-3-(vinyloxy)benzoate

HRID 595029Notes

Reaction equation

HRID 595029 reaction equation
N1C=CC=CC=1.C(B1OB(C=C)OB([CH:17]=[CH2:18])O1)=C.[OH:19][C:20]1[C:21]([N+:30]([O-:32])=[O:31])=[C:22]([CH:27]=[CH:28][CH:29]=1)[C:23]([O:25][CH3:26])=[O:24].N1C=CC=CC=1.C(O)(C(F)(F)F)=O>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.O.CO.ClCCl>[N+:30]([C:21]1[C:20]([O:19][CH:17]=[CH2:18])=[CH:29][CH:28]=[CH:27][C:22]=1[C:23]([O:25][CH3:26])=[O:24])([O-:32])=[O:31]

Participants

8

Reactant 4

HCID 1049PyridineHCID 6422Trifluoroacetic acidHCID 27348062,4,6-Trivinylboroxin-Pyridine ComplexHCID 13659833Methyl 3-hydroxy-2-nitrobenzoate

Product 1

HCID 90072113Methyl 2-nitro-3-(vinyloxy)benzoateYield 50.4%

Reagents, catalysts & solvents 3

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolventHCID 22242641Methanol--water (1/1)Solvent

Procedure

A mixture of copper (II) acetate (11.98 g, 65.9 mmol) and dichloromethane (80 mL) was stirred at room temperature for 10 minutes, before the addition of 2,4,6-trivinyl-1,3,5,2,4,6-trioxatriborinane compound with pyridine (1:1) (10.63 g, 44.2 mmol, 0.67 eq), methyl 3-hydroxy-2-nitrobenzoate (U.S. Publication No. 2012/0035194 A1 [0202]) (13 g, 65.9 mmol), pyridine (26.7 mL, 330 mmol), and molecular sieves (1 g). The resulting deep blue mixture was stirred at room temperature for 5 days, with the reaction mixture opened to the air. The reaction mixture was filtered through a pad of CELITE®, washing with dichloromethane. The filtrate was washed with 3M aqueous ammonium acetate (2×), water, and brine, and then dried and concentrated in vacuo. The crude product mixture was purified via silica gel chromatography (hexanes/EtOAc) to give Intermediate A1A (7.42 g, 33.2 mmol, 50.4% yield). HPLC: RT=2.487 min (H2O/MeOH with TFA, SunFire C18 3.5 μm, 2.1×30 mm, gradient=4 min, wavelength=220 nm); MS(ES): m/z=246 [M+Na]+; 1H NMR (400 MHz, chloroform-d) δ 7.77 (dd, J=7.8, 1.2 Hz, 1H), 7.55 (t, J=8.1 Hz, 1H), 7.38 (dd, J=8.4, 1.3 Hz, 1H), 6.61 (dd, J=13.6, 5.9 Hz, 1H), 4.95 (dd, J=13.6, 2.4 Hz, 1H), 4.69 (dd, J=5.9, 2.4 Hz, 1H), 3.93 (s, 3H), 1.56 (s, 1H), 0.03 (s, 1H).

Workup

  1. filtrationThe reaction mixture was filtered through a pad of CELITE®
  2. washwashing with dichloromethane
  3. washThe filtrate was washed with 3M aqueous ammonium acetate (2×), water, and brine
  4. customdried
  5. concentrationconcentrated in vacuo
  6. customThe crude product mixture was purified via silica gel chromatography (hexanes/EtOAc)
  7. customto give Intermediate A1A (7.42 g, 33.2 mmol, 50.4% yield)

Sources & evidence

ORD record
ord-446024c009c84109b7d5331137562b22
Source dataset
uspto-grants-2016_01
Patent number
US09242941B2

Reaction notes

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