Cesium fluoride → tert-Butyl 4-(4-(3-(cyclopropylmethyl)ureido)phenoxy)piperidine-1-carboxylate

HRID 515270Notes

Reaction equation

HRID 515270 reaction equation
[CH:1]1([CH2:4][NH:5][C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)=[O:7])[CH2:3][CH2:2]1.[F-].[Cs+].CS(O[CH:23]1[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]1)(=O)=O>CC(N(C)C)=O>[CH:1]1([CH2:4][NH:5][C:6](=[O:7])[NH:8][C:9]2[CH:10]=[CH:11][C:12]([O:15][CH:23]3[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]3)=[CH:13][CH:14]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 25953Cesium fluorideHCID 41848691-(tert-Butoxycarbonyl)-4-(methanesulfonyloxy)piperidineHCID 671944861-(Cyclopropylmethyl)-3-(4-hydroxyphenyl)urea

Product 1

HCID 67193130tert-Butyl 4-(4-(3-(cyclopropylmethyl)ureido)phenoxy)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Conditions

Temperature
85 °C

Procedure

To a stirring solution of 1-(cyclopropylmethyl)-3-(4-hydroxyphenyl)urea (6.79 mmol, 1.4 g) in dimethylacetamide (50 mL) was added cesium fluoride (20.36 mmol, 3.09 g) followed by a solution of tert-butyl 4-(methylsulfonyloxy)piperidine-1-carboxylate (8.15 mmol, 2.276 g) in dimethylacetamide (50 mL). The resulting suspension was heated to 85° C. overnight. The reaction mixture was filtered and the filtrate concentrated under vacuum. The residue was dissolved in dichloromethane and washed with water. The organic layer was separated, dried over magnesium sulfate and concentrated under vacuum. The residue was dissolved in dichloromethane and purified by column chromatography (eluent 2-8% methanol in dichloromethane) to afford the title compound. MS (ESI) m/z 390.0 [M+H]+

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationthe filtrate concentrated under vacuum
  3. dissolutionThe residue was dissolved in dichloromethane
  4. washwashed with water
  5. customThe organic layer was separated
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under vacuum
  8. dissolutionThe residue was dissolved in dichloromethane
  9. custompurified by column chromatography (eluent 2-8% methanol in dichloromethane)

Sources & evidence

ORD record
ord-a2d857227f6549dea464a5b5fcdc6da7
Source dataset
uspto-grants-2015_08
Patent number
US09108939B2

Reaction notes

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