Potassium Carbonate → 4-[4-(4-Methanesulfonyl-phenoxymethyl)-thiazol-2-yl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 871895Notes

Reaction equation

HRID 871895 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[S:15][CH:16]=[C:17]([CH2:19]Cl)[N:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:21][S:22]([C:25]1[CH:30]=[CH:29][C:28]([OH:31])=[CH:27][CH:26]=1)(=[O:24])=[O:23].C([O-])([O-])=O.[K+].[K+]>CC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[S:15][CH:16]=[C:17]([CH2:19][O:31][C:28]3[CH:27]=[CH:26][C:25]([S:22]([CH3:21])(=[O:24])=[O:23])=[CH:30][CH:29]=3)[N:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 1233504-(Methylsulfonyl)phenolHCID 57423790Tert-butyl 4-[4-(chloromethyl)-1,3-thiazol-2-yl]piperidine-1-carboxylate2×

Product 1

HCID 250241364-[4-(4-Methanesulfonyl-phenoxymethyl)-thiazol-2-yl]-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A mixture of 4-(4-Chloromethyl-thiazol-2-yl)-piperidine-1-carboxylic acid tert-butyl ester (Intermediate 1, 463 mg, 1.46 mmol), 4-methanesulfonyl-phenol (252 mg, 1.46 mmol) and K2CO3 (404 mg, 2.92 mmol) in acetone (25 mL) was heated under reflux overnight. After cooling, the solid was filtered through a pad of celite. The filtrate was concentrated in vacuo. The residue was purified on silica gel (EtOAc-hexanes, 1:1) to afford the desired product. 1H NMR (CDCl3): δ 7.88 (2H, d, J=8.8 Hz), 7.23 (1H, s), 7.12 (2H, d, J=8.8 Hz), 5.24 (2H, s), 4.21 (2H, br), 3.17 (1H, m), 3.04 (3H, s), 2.88 (2H, m), 2.11 (2H, m), 1.73 (2H, m), 1.47 (9H, s).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux overnight
  3. temperatureAfter cooling
  4. filtrationthe solid was filtered through a pad of celite
  5. concentrationThe filtrate was concentrated in vacuo
  6. customThe residue was purified on silica gel (EtOAc-hexanes, 1:1)

Sources & evidence

ORD record
ord-bce13501201a4826a3b2959b04a51b8c
Source dataset
uspto-grants-2015_03
Patent number
US08975258B2

Reaction notes

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