Benzaldehyde → HCID 24801159, compound

HRID 883174Notes

Reaction equation

HRID 883174 reaction equation
[CH2:1]([NH:8][C:9]([C:11]1[S:15][C:14]([N:16]2[CH2:21][CH2:20][CH2:19][CH2:18][C:17]2=[O:22])=[N:13][C:12]=1[CH3:23])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH:34](=[O:41])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.O>O1CCCC1.ClCCl>[CH2:1]([NH:8][C:9]([C:11]1[S:15][C:14]([N:16]2[CH2:21][CH2:20][CH2:19][CH:18]([CH:34]([OH:41])[C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[C:17]2=[O:22])=[N:13][C:12]=1[CH3:23])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 240BenzaldehydeHCID 962WaterHCID 2733832Lithium HexamethyldisilazideHCID 24799232N-benzyl-4-methyl-2-(2-oxopiperidin-1-yl)thiazole-5-carboxamide

Product 1

HCID 24801159HCID 24801159, compoundYield 3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of N-benzyl-4-methyl-2-(2-oxopiperidin-1-yl)thiazole-5-carboxamide (0.25 g, 0.76 mmol) in anhydrous tetrahydrofuran (10 mL) at −78° C. was added lithium bis(trimethylsilyl)amide in tetrahydrofuran (0.83 mL, 0.83 mmol) dropwise. The reaction mixture was stirred at −78° C. for 5 minutes, followed by the dropwise addition of benzaldehyde (0.077 mL, 0.76 mmol). The resulting mixture was slowly warmed to −30° C. over 30 minutes, followed by the addition of water (5 mL) and extraction with dichloromethane (3×10 mL). The combined organic solution was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified by column chromatography (ethyl acetate/hexanes (1/1)) to afford the title compound as a white solid (0.010 g, 3%): mp 74-75° C. (hexanes/ethyl acetate); 1H NMR (300 MHz, CDCl3) δ 7.42-7.22 (m, 10H), 6.01 (t, J=5.5 Hz, 1H), 5.63 (d, J=2.5 Hz, 1H), 4.57 (d, J=5.5 Hz, 2H), 4.38-4.30 (m, 1H), 3.91-3.81 (m, 1H), 2.88-2.82 (m, 1H), 2.63 (s, 3H), 2.09-1.51 (m, 4H); 13C NMR (75 MHz, CDCl3) δ 171.7, 162.6, 152.0, 141.4, 137.9, 128.8, 128.6, 128.4, 127.9, 127.7, 127.5, 125.8, 119.7, 72.7, 49.8, 48.0, 44.1, 21.6, 19.4, 17.3; MS (ES+) m/z 436.2 (M+1).

Workup

  1. temperatureThe resulting mixture was slowly warmed to −30° C. over 30 minutes
  2. dry with materialThe combined organic solution was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated in vacuo
  5. customthe residue was purified by column chromatography (ethyl acetate/hexanes (1/1))

Sources & evidence

ORD record
ord-c937bc7a802d47a69905df41cc25228a
Source dataset
uspto-grants-2012_08
Patent number
US08236835B2

Reaction notes

Loading…