Potassium Carbonate → 4-Chlorophenyl 3-(2-fluoropropan-2-yl)isoxazol-5-ylcarbamate

HRID 1918024Notes

Reaction equation

HRID 1918024 reaction equation
[F:1][C:2]([C:5]1[CH:9]=[C:8]([NH2:10])[O:7][N:6]=1)([CH3:4])[CH3:3].C(=O)([O-])[O-].[K+].[K+].Cl[C:18]([O:20][C:21]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=1)=[O:19]>C1COCC1>[F:1][C:2]([C:5]1[CH:9]=[C:8]([NH:10][C:18](=[O:19])[O:20][C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)[O:7][N:6]=1)([CH3:4])[CH3:3]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 1390594-Chlorophenyl chloroformate2×HCID 534020703-(2-Fluoropropan-2-yl)-1,2-oxazol-5-amine

Product 1

HCID 668775214-Chlorophenyl 3-(2-fluoropropan-2-yl)isoxazol-5-ylcarbamateYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3-(2-fluoropropan-2-yl)isoxazol-5-amine (11.26 g, 78.19 mmol) described in Example 42A in THF (300 mL) was treated with potassium carbonate (21.58 g, 156 mmol) and p-chlorophenyl chloroformate (14.94 g, 78.19 mmol). After stirring at rt for 1 h, additional p-chlorophenyl chloroformate (7.5 g, 39.26 mmol) was introduced, and the reaction mixture was stirred at rt overnight. The mixture was filtered through a celite pad, washed with ethyl acetate and concentrated to dryness. The residue was taken into ethyl acetate, washed with brine, and the organics dried (MgSO4) and concentrated. The residue was purified by silica gel chromatography (eluting with 10 to 50% ethyl acetate in hexanes) to give 4-chlorophenyl 3-(2-fluoropropan-2-yl)isoxazol-5-ylcarbamate (16.51 g, 71%) as a cream solid. 1H NMR (300 MHz, CDCl3) δ 7.87 (brs, 1H), 7.36-7.41 (m, 2H), 7.13-7.17 (m, 2H), 6.27 (s, 1H), 1.74 (d, J=21 Hz, 6H); LC-MS (ESI) m/z 299 (M+H)+.

Workup

  1. stirringthe reaction mixture was stirred at rt overnight
  2. filtrationThe mixture was filtered through a celite pad
  3. washwashed with ethyl acetate
  4. concentrationconcentrated to dryness
  5. washwashed with brine
  6. dry with materialthe organics dried (MgSO4)
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography (eluting with 10 to 50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-9446e6d427104bc79e894b2edfb78a05
Source dataset
uspto-grants-2013_12
Patent number
US08618289B2

Reaction notes

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