Water → HCID 89726761, compound

HRID 1777768Notes

Reaction equation

HRID 1777768 reaction equation
F[C:2]1[CH:3]=[CH:4][C:5]([N+:9]([O-:11])=[O:10])=[C:6]([CH:8]=1)[NH2:7].[C:12]([N:19]1[CH2:22][CH:21]([OH:23])[CH2:20]1)([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].[H-].[Na+].O>CN(C=O)C.CC(=O)OCC.O.C1(C)C=CC=CC=1>[C:15]([O:14][C:12]([N:19]1[CH2:22][CH:21]([O:23][C:2]2[CH:3]=[CH:4][C:5]([N+:9]([O-:11])=[O:10])=[C:6]([NH2:7])[CH:8]=2)[CH2:20]1)=[O:13])([CH3:18])([CH3:16])[CH3:17]

Participants

8

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 753995-Fluoro-2-nitroanilineHCID 2756801Tert-butyl 3-hydroxyazetidine-1-carboxylate

Product 1

HCID 89726761HCID 89726761, compoundYield 84%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 22728543Water ethylacetateSolvent

Conditions

Temperature
100 °C

Procedure

A flask was charged with 5-fluoro-2-nitroaniline (329 mg), 1-Boc-3-hydroxyazetidine (346 mg) and NaH (65% in oil, 62.4 mg) in DMF (6 mL). The mixture was heated at 100° C. for 7 h, cooled down, and diluted water. The solvent was coevaporated with toluene. The residue was taken up in EA/water and the org. layer was evaporated in vacuo. The residue was purified by CC (Biotage, SNAP 25 g cartridge, solvent A: Hept; solvent B: EA; gradient in % B: 8 for 4CV, 8 to 66 over 10CV, 66 for 2CV) to afford 519 mg of orange foam. LC-MS (B): tR=0.88 min. 1H-NMR (CDCl3): 8.11 (d, 1H, 9.5 Hz); 6.22 (s, NH2); 6.19 (dd, 1H, 2.6 Hz and 9.5 Hz); 5.97 (d, 1H, 2.5 Hz); 4.90 (m, 1H); 4.33 (m, 2H); 4.02 (m, 2H); 1.47 (s, 9H).

Workup

  1. temperaturecooled down
  2. customlayer was evaporated in vacuo
  3. customThe residue was purified by CC (Biotage, SNAP 25 g cartridge, solvent A: Hept; solvent B: EA; gradient in % B: 8 for 4CV, 8 to 66 over 10CV, 66 for 2CV)

Sources & evidence

ORD record
ord-338df9a8427b4296b17dca9eae852fd0
Source dataset
uspto-grants-2016_02
Patent number
US09266876B2

Reaction notes

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