Cesium carbonate → 2-Methyl-4-(1-(5-phenyl-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)benzaldehyde

HRID 2359385Notes

Reaction equation

HRID 2359385 reaction equation
[OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[C:4]([CH3:10])[CH:3]=1.CS(O[CH:16]1[CH2:19][N:18]([C:20]([C:22]2[O:23][C:24]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[N:25][N:26]=2)=[O:21])[CH2:17]1)(=O)=O.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.C(Cl)Cl>[CH3:10][C:4]1[CH:3]=[C:2]([O:1][CH:16]2[CH2:17][N:18]([C:20]([C:22]3[O:23][C:24]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)=[N:25][N:26]=3)=[O:21])[CH2:19]2)[CH:9]=[CH:8][C:5]=1[CH:6]=[O:7]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 4581854-Hydroxy-2-methylbenzaldehydeHCID 580430991-(5-Phenyl-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yl methanesulfonate

Product 1

HCID 580431052-Methyl-4-(1-(5-phenyl-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)benzaldehydeYield 72%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 4-hydroxy-2-methylbenzaldehyde (0.11 g, 0.79 mmol) and 1-(5-phenyl-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yl methanesulfonate (0.20 g, 0.62 mmol, Intermediate IB above) in DMF (10 mL) under nitrogen was added Cs2CO3 (0.24 g, 0.74 mmol). The mixture was stirred at 90° C. for 20 h, cooled to RT and then diluted with DCM. The solids were filtered off and the filtrate was evaporated. The product was purified on two occasions by preparative HPLC (Kromasil, C8) eluting with a gradient of acetonitrile and a mixture of acetic acid and water (0.2%). The pure fractions were combined and concentrated. The aqueous residues were extracted with DCM and the organic solutions were evaporated. There was obtained 162 mg (72%) of the title compound as a solid. 1H NMR (500 MHz, CDCl3): δ 2.66 (s, 3H), 4.34 (d, 1H), 4.69 (dd, 1H), 4.76 (d, 1H), 5.17 (m, 2H), 6.64 (d, 1H), 6.72 (dd, 1H), 7.53 (t, 2H), 7.59 (t, 1H), 7.78 (d, 1H), 8.15 (d, 1H), 10.14 (s, 1H), MS (APCI+) m/z 364 [M+H]+.

Workup

  1. temperaturecooled to RT
  2. filtrationThe solids were filtered off
  3. customthe filtrate was evaporated
  4. customThe product was purified on two occasions by preparative HPLC (Kromasil, C8)
  5. washeluting with a gradient of acetonitrile
  6. additiona mixture of acetic acid and water (0.2%)
  7. concentrationconcentrated
  8. extractionThe aqueous residues were extracted with DCM
  9. customthe organic solutions were evaporated

Sources & evidence

ORD record
ord-5a46b762b11f414cb0427d9583db21f8
Source dataset
uspto-grants-2014_04
Patent number
US08685958B2

Reaction notes

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