Cesium carbonate → tert-Butyl 4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)piperidine-1-carboxylate

HRID 341171Notes

Reaction equation

HRID 341171 reaction equation
[CH3:1][C:2]1([CH3:16])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:10]=[C:11]([OH:15])[CH:12]=[CH:13][CH:14]=2)[O:3]1.C([O-])([O-])=O.[Cs+].[Cs+].[C:23]([O:27][C:28]([N:30]1[CH2:35][CH2:34][CH:33](OS(C)(=O)=O)[CH2:32][CH2:31]1)=[O:29])([CH3:26])([CH3:25])[CH3:24]>CN1C(=O)CCC1.O>[C:23]([O:27][C:28]([N:30]1[CH2:35][CH2:34][CH:33]([O:15][C:11]2[CH:12]=[CH:13][CH:14]=[C:9]([B:4]3[O:3][C:2]([CH3:16])([CH3:1])[C:6]([CH3:7])([CH3:8])[O:5]3)[CH:10]=2)[CH2:32][CH2:31]1)=[O:29])([CH3:26])([CH3:24])[CH3:25]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27346233-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 41848691-(tert-Butoxycarbonyl)-4-(methanesulfonyloxy)piperidine

Product 1

HCID 17758346tert-Butyl 4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)piperidine-1-carboxylateYield 51.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenol (10.0 g, 45.4 mmol, 1.0 equiv) in NMP (100 ml) was added Cs2CO3 (44.4 g), 136.3 mmol, 3.0 equiv) and 4-methanesulfonyloxy-piperidine-1-carboxylic acid tert-butyl ester (19.0 g, 68.2 mmol, 1.5 equiv). The reaction mixture was heated to 80° C. and monitored until complete. The reaction mixture was cooled to room temperature, diluted with water and extracted with EtOAc. The organic layer was washed successively with 2N KOH, water, brine, dried (MgSO4), filtered and concentrated under reduced pressure. The target molecule was purified by column chromatography (SiO2), eluted with 5→30% EtOAc-petrol to afford a colourless liquid (9.5 g) that crystallised on standing. 1H NMR (400 MHz, CDCl3): 7.42 (1H, d), 7.37 (1H, d), 7.31 (1H, t), 7.03 (1H, dd), 4.61-4.49 (1H, m), 3.76-3.62 (2H, m), 3.47-3.32 (2H, m), 1.99-1.86 (2H, m), 1.86-1.70 (2H, m), 1.49 (9H, s).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed successively with 2N KOH, water, brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe target molecule was purified by column chromatography (SiO2)
  8. washeluted with 5→30% EtOAc-petrol

Sources & evidence

ORD record
ord-a1251b0bd1304dd580f6d38d8c108f48
Source dataset
uspto-grants-2014_11
Patent number
US08895745B2

Reaction notes

Loading…