Diisopropylethylamine → 2-{1-[2-(2,5-Dimethyl-phenyl)-acetyl]-piperidin-4-yl}-thiazole-4-carboxylic acid ethyl ester

HRID 1042055Notes

Reaction equation

HRID 1042055 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[CH2:9][C:10]([OH:12])=O.C(N(C(C)C)CC)(C)C.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[CH2:44]([O:46][C:47]([C:49]1[N:50]=[C:51]([CH:54]2[CH2:59][CH2:58][NH:57][CH2:56][CH2:55]2)[S:52][CH:53]=1)=[O:48])[CH3:45]>CN(C=O)C>[CH2:44]([O:46][C:47]([C:49]1[N:50]=[C:51]([CH:54]2[CH2:59][CH2:58][N:57]([C:10](=[O:12])[CH2:9][C:3]3[CH:4]=[C:5]([CH3:8])[CH:6]=[CH:7][C:2]=3[CH3:1])[CH2:56][CH2:55]2)[S:52][CH:53]=1)=[O:48])[CH3:45]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 836152,5-Dimethylphenylacetic acidHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 579359592-Piperidine-4-yl-thiazole-4-carboxylic acid ethyl ester

Product 1

HCID 669564672-{1-[2-(2,5-Dimethyl-phenyl)-acetyl]-piperidin-4-yl}-thiazole-4-carboxylic acid ethyl esterYield 98.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2,5-dimethylphenylacetic acid (5.45 g, 27.4 mmol) in DMF (80 mL) is added diisopropylethylamine (85.4 mL, 411.32 mmol), followed by O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (12.8 g, 32.9 mmol) at 0° C. After stirring 15 min at RT, 2-piperidin-4-yl-thiazole-4-carboxylic acid ethyl ester (6.59 g, 27.4 mmol) is added to the reaction mixture. After stirring overnight at RT, solvent is evaporated and the resulting yellow oil is dissolved in ethylacetate (500 mL), washed with aqueous saturated sodium bicarbonate solution (500 mL) and the aqueous phase is re-extracted with ethylacetate (100 mL). The combined organic layers are washed with 0.5M HCl solution (400 mL) and brine (400 mL), dried over sodium sulfate, filtered, and evaporated under reduced pressure to give 2-{1-[2-(2,5-dimethyl-phenyl)-acetyl]-piperidin-4-yl}-thiazole-4-carboxylic acid ethyl ester (10.46 g, 98%), which can be used in the next step without further purification. 1H-NMR (400 MHz, CDCl3): δ=1.41 (t, 3H), 1.52-1.82 (m, 2H), 2.10-2.22 (m, 2H), 2.25 (s, 3H), 2.30 (s, 3H), 2.73-2.86 (m, 1H), 3.08-3.22 (m, 1H), 3.29-3.40 (m, 1H), 3.68 (s, 2H), 3.8-3.95 (m, 1H), 4.38-4.42 (q, 2H), 4.73-4.88 (m, 1H), 6.96 (s, 1H), 6.98-7.01 (d, 1H), 7.08 (d, 1H), 8.10 (s, 1H). MS: m/z=387 (M+1).

Workup

  1. stirringAfter stirring overnight at RT
  2. customsolvent is evaporated
  3. dissolutionthe resulting yellow oil is dissolved in ethylacetate (500 mL)
  4. washwashed with aqueous saturated sodium bicarbonate solution (500 mL)
  5. extractionthe aqueous phase is re-extracted with ethylacetate (100 mL)
  6. washThe combined organic layers are washed with 0.5M HCl solution (400 mL) and brine (400 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-839b1d10ca4c496d87550ee94478e37f
Source dataset
uspto-grants-2013_10
Patent number
US08557821B2

Reaction notes

Loading…