Diisopropylethylamine → 4-(4-tert-Butoxycarbonylamino-piperidine-1-sulfonyl)-2-fluoro-benzoic acid methyl ester

HRID 337216Notes

Reaction equation

HRID 337216 reaction equation
C(N(C(C)C)CC)(C)C.[C:10]([O:14][C:15](=[O:23])[NH:16][CH:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1)([CH3:13])([CH3:12])[CH3:11].[CH3:24][O:25][C:26](=[O:38])[C:27]1[CH:32]=[CH:31][C:30]([S:33](Cl)(=[O:35])=[O:34])=[CH:29][C:28]=1[F:37]>C(Cl)Cl>[CH3:24][O:25][C:26](=[O:38])[C:27]1[CH:32]=[CH:31][C:30]([S:33]([N:20]2[CH2:21][CH2:22][CH:17]([NH:16][C:15]([O:14][C:10]([CH3:13])([CH3:11])[CH3:12])=[O:23])[CH2:18][CH2:19]2)(=[O:34])=[O:35])=[CH:29][C:28]=1[F:37]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 7238334-(N-Boc-amino)piperidineHCID 57732146Methyl 4-(chlorosulfonyl)-2-fluorobenzoate

Product 1

HCID 710602664-(4-tert-Butoxycarbonylamino-piperidine-1-sulfonyl)-2-fluoro-benzoic acid methyl esterYield 94.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Diisopropylethylamine (3.2 ml, 18.5 mmol) was added in one portion to a stirred solution of piperidin-4-yl-carbamic acid tert-butyl ester (0.5 g, 2.5 mmol) in DCM (10 ml) at room temperature. To this mixture was added 4-chlorosulfonyl-2-fluoro-benzoic acid methyl ester (0.6 g, 2.5 mmol) in one portion and the mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour. After this time the mixture was diluted with DCM (50 ml) and washed sequentially with HCl (1M solution, 10 ml), NaOH (1M solution, 10 ml) and brine (10 ml). The organic layer was separated, dried (MgSO4), filtered and concentrated. The resulting residue was purified by flash column chromatography (elution: 98% DCM, 2% Methanol) to give the title compound (0.98 g, 87% yield) as a white solid. Tr=2.08 min m/z (ES+) (M+Na+) 439.

Workup

  1. washwashed sequentially with HCl (1M solution, 10 ml), NaOH (1M solution, 10 ml) and brine (10 ml)
  2. customThe organic layer was separated
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting residue was purified by flash column chromatography (elution: 98% DCM, 2% Methanol)

Sources & evidence

ORD record
ord-8038d215d4ae41dca06eaade5d338aea
Source dataset
uspto-grants-2014_11
Patent number
US08889716B2

Reaction notes

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