Cesium carbonate → 3-{[6-(Azetidin-1-ylcarbonyl)pyridin-3-yl]oxy}-5-[(phenylmethyl)oxy]benzoic acid

HRID 600531Notes

Reaction equation

HRID 600531 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:11]=1)[C:5]([O:7]C)=[O:6].[N:20]1([C:24]([C:26]2[CH:31]=[CH:30][C:29](Br)=[CH:28][N:27]=2)=[O:25])[CH2:23][CH2:22][CH2:21]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(N(C)C)=O>[N:20]1([C:24]([C:26]2[N:27]=[CH:28][C:29]([O:1][C:2]3[CH:3]=[C:4]([CH:9]=[C:10]([O:12][CH2:13][C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=4)[CH:11]=3)[C:5]([OH:7])=[O:6])=[CH:30][CH:31]=2)=[O:25])[CH2:23][CH2:22][CH2:21]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 7472028Methyl 3-(benzyloxy)-5-hydroxybenzoateHCID 536296172-(Azetidin-1-ylcarbonyl)-5-bromopyridine

Product 1

HCID 536297013-{[6-(Azetidin-1-ylcarbonyl)pyridin-3-yl]oxy}-5-[(phenylmethyl)oxy]benzoic acidYield 76%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

A mixture of methyl 3-hydroxy-5-phenylmethoxy-benzoate (CAS no. 54915-31-0) (5.16 g, 20 mmol), azetidin-1-yl-(5-bromopyridin-2-yl)methanone (CAS no. 845306-16-3, Intermediate 34) (5.3 g, 22 mmol), caesium carbonate (19.6 g, 60 mmol) and tris(triphenylphosphine)copper bromide (CAS no. 15709-74-7) (3.73 g, 4 mmol) in DMA (100 mL) was stirred at 160° C. for 6 hours. The DMA was evaporated under reduced pressure and the residue was dissolved in water (200 mL), washed with ethyl acetate (3×50 mL), acidified with 2N hydrochloric acid and extracted with ethyl acetate (3×100 mL). The organic layer washed with water (2×20 mL) and brine (20 mL), dried (MgSO4) and the solvent removed under reduced pressure to afford the product (6.18 g, 76%). 1H NMR δ (400 MHz, CDCl3) 2.29 (s, 2H), 4.20 (s, 2H), 4.64 (s, 2H), 5.04 (s, 2H), 6.83 (s, 1H), 7.22-7.44 (m, 7H), 7.49 (s, 1H), 7.79-8.63 (m, 2H); m/z 405 (M+H)+.

Workup

  1. customThe DMA was evaporated under reduced pressure
  2. dissolutionthe residue was dissolved in water (200 mL)
  3. washwashed with ethyl acetate (3×50 mL)
  4. extractionextracted with ethyl acetate (3×100 mL)
  5. washThe organic layer washed with water (2×20 mL) and brine (20 mL)
  6. dry with materialdried (MgSO4)
  7. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-43e96ed4062d42dd9e047ce8cbb3313c
Source dataset
uspto-grants-2011_03
Patent number
US07902200B2

Reaction notes

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