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

HRID 599473Notes

Reaction equation

HRID 599473 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)C(C)C)(C)C.[CH3:33][O:34][C:35]([C:37]1[N:38]([CH3:46])[C:39]([S:42](Cl)(=[O:44])=[O:43])=[CH:40][CH:41]=1)=[O:36]>C1COCC1.C(OCC)(=O)C>[CH3:33][O:34][C:35]([C:37]1[N:38]([CH3:46])[C:39]([S:42]([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:44])=[O:43])=[CH:40][CH:41]=1)=[O:36]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 2736899Methyl 5-(chlorosulfonyl)-1-methyl-1H-pyrrole-2-carboxylateHCID 86635427HCID 86635427, 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 57.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2,6-di-tert-butyl-4-(piperidin-4-ylsulfanyl)-phenol hydrochloride (Ex. 3c, 5.4 g) in 44 mL of THF at room temperature was added N,N-diisopropylethylamine (8.8 mL), followed by 5-chlorosulfonyl-1-methyl-1H-pyrrole-2-carboxylic acid methyl ester (4 g). The mixture was stirred at room temperature for 18 h and then diluted with ethyl acetate and washed twice with 1 N HCl (aq), and once with brine. After concentration of the organic extracts, the crude solid was triturated with 15% ethyl acetate in hexanes to give 4.5 g of 5-[4-(3,5-di-tert-butyl-4-hydroxy-phenylsulfanyl)-piperidine-1-sulfonyl]-1-methyl-1H-pyrrole-2-carboxylic acid methyl ester as an off-white solid, mp 181-183° C. 1H-NMR (300 MHz, CDCl3): δ 7.23 (s, 2H), 7.17 (d, 1H, J=1.5 Hz), 7.09 (d, 1H, J=1.2 Hz), 5.30 (s, 1H), 3.96 (s, 3H), 3.83 (s, 3H), 3.60-3.54 (m, 2H), 2.80-2.74 (m, 1H), 2.54-2.45 (m, 2H), 2.03-1.97 (m, 2H), 1.73-1.67 (m, 2H), 1.41 (s, 18H).

Workup

  1. washwashed twice with 1 N HCl (aq)
  2. customAfter concentration of the organic extracts, the crude solid was triturated with 15% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-56518f5b2ddd4110a733071ba2917bc1
Source dataset
uspto-grants-2011_03
Patent number
US07897776B2

Reaction notes

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