Isopropenyl chloroformate → prop-1-en-2-yl 2-fluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)phenylcarbamate

HRID 1098604Notes

Reaction equation

HRID 1098604 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]([C:15]3[CH:16]=[N:17][N:18]([CH3:20])[CH:19]=3)[CH:10]=2)[CH:5]=[CH:4][C:3]=1[NH2:21].C([O-])(O)=O.[Na+].Cl[C:28]([O:30][C:31]([CH3:33])=[CH2:32])=[O:29]>CCOC(C)=O>[F:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]([C:15]3[CH:16]=[N:17][N:18]([CH3:20])[CH:19]=3)[CH:10]=2)[CH:5]=[CH:4][C:3]=1[NH:21][C:28](=[O:29])[O:30][C:31]([CH3:33])=[CH2:32]

Participants

5

Reactant 3

HCID 93846Isopropenyl chloroformateHCID 516892Sodium BicarbonateHCID 594583192-fluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)benzenamine

Product 1

HCID 66729122prop-1-en-2-yl 2-fluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)phenylcarbamateYield 90%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of Example A1 (2.0 g, 7.04 mmol) and saturated aq NaHCO3 (100 mL) in EtOAc (100 mL) was cooled in an ice bath and treated with isopropenyl chloroformate (1.6 mL, 14.64 mmol). The reaction mixture was allowed to slowly warm to RT overnight. The organic layer was separated and washed with sat aq NaHCO3 (25 mL) and brine (25 mL), dried (MgSO4), concentrated in vacuo and was re-crystallized (diethylether) to provide prop-1-en-2-yl 2-fluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)phenylcarbamate (2.32 g, 90% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.69 (br s, 1 H), 8.38 (d, J=5.6 Hz, 1 H), 8.26 (s, 1 H), 7.96 (d, J=0.8 Hz, 1 H), 7.67 (br t, J=8.4 Hz, 1 H), 7.27 (d, J=2.4 Hz, 1 H), 7.22 (dd, J=11.2, 2.4 Hz, 1 H), 7.00 (m, 1 H), 6.69 (dd, J=5.6, 2.4 Hz, 1 H), 4.74 (m, 1 H), 4.72 (s, 1 H), 3.84 (s, 3 H), 1.92 (s, 3H); MS (ESI) m/z: 369.1(M+H+).

Workup

  1. customThe organic layer was separated
  2. washwashed with sat aq NaHCO3 (25 mL) and brine (25 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customwas re-crystallized (diethylether)

Sources & evidence

ORD record
ord-420e7dde37a946bc891ab9f72daa43bd
Source dataset
uspto-grants-2012_03
Patent number
US08143293B2

Reaction notes

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