Triethylamine → 2-[4-(3,5-di-tert-butyl-4-hydroxy-phenylsulfanyl)-piperidine-1-sulfonyl]-3H-imidazole-4-carboxylic acid ethyl ester

HRID 599478Notes

Reaction equation

HRID 599478 reaction equation
Cl.[C:2]([C:6]1[CH:11]=[C:10]([S:12][CH:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)[CH:9]=[C:8]([C:19]([CH3:22])([CH3:21])[CH3:20])[C:7]=1[OH:23])([CH3:5])([CH3:4])[CH3:3].C(N(CC)CC)C.[CH2:31]([O:33][C:34]([C:36]1[NH:37][C:38]([S:41](Cl)(=[O:43])=[O:42])=[N:39][CH:40]=1)=[O:35])[CH3:32]>ClCCl>[CH2:31]([O:33][C:34]([C:36]1[NH:37][C:38]([S:41]([N:16]2[CH2:17][CH2:18][CH:13]([S:12][C:10]3[CH:9]=[C:8]([C:19]([CH3:22])([CH3:21])[CH3:20])[C:7]([OH:23])=[C:6]([C:2]([CH3:5])([CH3:4])[CH3:3])[CH:11]=3)[CH2:14][CH2:15]2)(=[O:42])=[O:43])=[N:39][CH:40]=1)=[O:35])[CH3:32]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 55280183Ethyl 2-(chlorosulfonyl)-1H-imidazole-5-carboxylateHCID 86635427HCID 86635427, compound

Product 1

HCID 866354322-[4-(3,5-di-tert-butyl-4-hydroxy-phenylsulfanyl)-piperidine-1-sulfonyl]-3H-imidazole-4-carboxylic acid ethyl esterYield 66%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To 2,6-di-tert-butyl-4-(piperidin-4-ylsulfanyl)-phenol hydrochloride (Ex. 3c, 405 mg, 1.13 mmol) in 6 mL of dichloromethane was added triethylamine (303 mg, 3 mmol). After stirring for 3 min, 2-chlorosulfonyl-3H-imidazole-4-carboxylic acid ethyl ester (Ex. 8a, 270 mg, 1.13 mmol) in 2 mL of dichloromethane was added. The reaction was stirred for 2 h and then quenched with saturated NaH2PO4 (30 mL). The mixture was extracted with Ethyl acetate (50+30 mL) and the combined organic phase was washed with water (50 mL), dried over Na2SO4, and concentrated under reduced pressure. Chromatography (5-70% Ethyl acetate/hexanes) gave 2-[4-(3,5-di-tert-butyl-4-hydroxy-phenylsulfanyl)-piperidine-1-sulfonyl]-3H-imidazole-4-carboxylic acid ethyl ester as a yellow foamy solid (390 mg, 66%). 1H NMR (400 MHz, CDCl3): δ 10.92 (bs, 0.5H), 10.71 (bs, 0.5H), 7.77 (bs, 1H), 7.25 (s, 2H), 5.30 (s, 1H), 4.39 (q, J=7.2 Hz, 2H), 3.80 (dt, J=12.4, 4.4 Hz, 2H), 3.00-2.88 (m, 3H), 2.02-1.98 (m, 2H), 1.68 (m, 2H), 1.42 (s, 18H), 1.38 (t, J=7.2 Hz, 3H). 13C NMR: δ 154.6, 136.9, 132.0, 122.0, 60.9, 46.1, 44.5, 34.5, 31.7, 30.4, 14.5. ESI/CI-MS m/z 525 ([M+H]+), 523 ([M−H]−).

Workup

  1. stirringThe reaction was stirred for 2 h
  2. customquenched with saturated NaH2PO4 (30 mL)
  3. extractionThe mixture was extracted with Ethyl acetate (50+30 mL)
  4. washthe combined organic phase was washed with water (50 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-2c6b6cc44c5b4a5fbce008277552bdf2
Source dataset
uspto-grants-2011_03
Patent number
US07897776B2

Reaction notes

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