Sodium hydride → tert-butyl cis-3-fluoro-4-((4-(N-isobutyl-N-(5-isopropylpyridin-2-yl)sulfamoyl)phenoxy)methyl)piperidine-1-carboxylate

HRID 594138Notes

Reaction equation

HRID 594138 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH2:21][CH:22]([CH3:24])[CH3:23])[C:12]2[CH:17]=[CH:16][C:15]([CH:18]([CH3:20])[CH3:19])=[CH:14][N:13]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[H-].[Na+].[F:27][C@H:28]1[C@@H:33]([CH2:34][OH:35])[CH2:32][CH2:31][N:30]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:29]1>CN(C)C=O>[F:27][C@H:28]1[C@@H:33]([CH2:34][O:35][C:2]2[CH:7]=[CH:6][C:5]([S:8](=[O:9])(=[O:10])[N:11]([CH2:21][CH:22]([CH3:23])[CH3:24])[C:12]3[CH:17]=[CH:16][C:15]([CH:18]([CH3:20])[CH3:19])=[CH:14][N:13]=3)=[CH:4][CH:3]=2)[CH2:32][CH2:31][N:30]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:29]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 89875921(3S,4R)-rel-tert-Butyl 3-fluoro-4-(hydroxymethyl)piperidine-1-carboxylateHCID 898760314-fluoro-N-isobutyl-N-(5-isopropylpyridin-2-yl)benzenesulfonamide

Product 1

HCID 117925812tert-butyl cis-3-fluoro-4-((4-(N-isobutyl-N-(5-isopropylpyridin-2-yl)sulfamoyl)phenoxy)methyl)piperidine-1-carboxylateYield 83.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-fluoro-N-isobutyl-N-(5-isopropylpyridin-2-yl)benzenesulfonamide (30 mg, 0.10 mmol) was dissolved in N,N-dimethylformamide (DMF) (3 mL) and to this solution was added sodium hydride (2 mg, 0.10 mmol, 60% wt in mineral oil) followed by tert-butyl cis-3-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate (24 mg, 0.10 mmol). The reaction was stirred for 3 hours at room temperature, under nitrogen, then quenched with water and concentrated in vacuo. The crude product was extracted to the organic phase of an aqueous workup between ethyl acetate and water. The organic phase was then passed through a hydrophobic frit and concentrated in vacuo to give the title compound (47 mg). LCMS (2 min, formic) Rt 1.50 min, m/z (ES+) 564 (M+H).

Workup

  1. customquenched with water
  2. concentrationconcentrated in vacuo
  3. extractionThe crude product was extracted to the organic phase of an aqueous workup between ethyl acetate and water
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8ee443171bb944fcb96a70947d88ea08
Source dataset
uspto-grants-2016_01
Patent number
US09242972B2

Reaction notes

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