Diisopropylethylamine → 5-[4-(3,5-di-tert-butyl-4-hydroxy-phenylsulfanyl)-piperidine-1-sulfonyl]-1-methyl-1H-pyrrole-2-carboxylic acid methyl ester

HRID 599474Notes

Reaction equation

HRID 599474 reaction equation
[C:1]([C:5]1[CH:10]=[C:9]([S:11][CH:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)[CH:8]=[C:7]([C:18]([CH3:21])([CH3:20])[CH3:19])[C:6]=1[OH:22])([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.[CH3:32][O:33][C:34]([C:36]1[N:37]([CH3:45])[C:38]([S:41](Cl)(=[O:43])=[O:42])=[CH:39][CH:40]=1)=[O:35]>C1COCC1.C(OCC)(=O)C.O>[CH3:32][O:33][C:34]([C:36]1[N:37]([CH3:45])[C:38]([S:41]([N:15]2[CH2:16][CH2:17][CH:12]([S:11][C:9]3[CH:8]=[C:7]([C:18]([CH3:21])([CH3:20])[CH3:19])[C:6]([OH:22])=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[CH:10]=3)[CH2:13][CH2:14]2)(=[O:43])=[O:42])=[CH:39][CH:40]=1)=[O:35]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 2736899Methyl 5-(chlorosulfonyl)-1-methyl-1H-pyrrole-2-carboxylateHCID 86635428HCID 86635428, compound

Product 1

HCID 866354305-[4-(3,5-di-tert-butyl-4-hydroxy-phenylsulfanyl)-piperidine-1-sulfonyl]-1-methyl-1H-pyrrole-2-carboxylic acid methyl esterYield 98.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Alternatively, to a solution of 2,6-di-tert-butyl-4-(piperidin-4-ylsulfanyl)-phenol (Ex. 3d, 48.0 g, 0.15 moles) in THF (1000 mL) was added diisopropylethyl amine (39.0 mL, 0.22 moles) and methyl-5-(chlorosulfonyl)-1-methyl-1H-pyrrole-2-carboxylate (35.5 g, 0.15 moles) and the resulting solution was stirred at room temperature for 5 hours. Upon completion, as determined by HPLC, the reaction was diluted with ethyl acetate (500 mL) and water (500 mL). The layers were cut and the organic layer was washed with 1N HCl (500 mL) and 6% brine (2×500 mL), and concentrated under reduced pressure to afford 77.2 g (98.8%) of 5-[4-(3,5-di-tert-butyl-4-hydroxy-phenylsulfanyl)-piperidine-1-sulfonyl]-1-methyl-1H-pyrrole-2-carboxylic acid methyl ester as a white solid, mp 185-187° C. 1H-NMR (400 MHz, CDCl3): δ 7.23 (s, 2H), 7.17 (d, 1H, J=1.6 Hz), 7.09 (d, 1H, J=2.0 Hz), 5.29 (s, 1H), 3.96 (s, 3H), 3.84 (s, 3H), 3.57 (m, 2H), 2.79 (m, 1H), 2.50 (m, 2H), 1.99 (m, 2H), 1.70 (m, 2H), 1.42 (s, 18H). HRMS (ESI) Calcd. for C26H38N2O5S2, 522.2222 (M+). Found: 522.2228. Anal. Calcd. for C26H38N2O5S2: C, 59.74; H, 7.33; N, 5.36; S, 12.27. Found: C, 59.48; H, 7.50; N, 5.22; S, 12.05.

Workup

  1. washthe organic layer was washed with 1N HCl (500 mL) and 6% brine (2×500 mL)
  2. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d40585d96c60429b9fd181f3d30fbb3e
Source dataset
uspto-grants-2011_03
Patent number
US07897776B2

Reaction notes

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