Hydrochloric Acid → 3-Chloro-4-((4-fluorotetrahydro-2h-pyran-4-yl)methoxy)benzenesulfonamide

HRID 573187Notes

Reaction equation

HRID 573187 reaction equation
[F:1][C:2]1([CH2:8][OH:9])[CH2:7][CH2:6][O:5][CH2:4][CH2:3]1.[H-].[Na+].[Cl:12][C:13]1[CH:14]=[C:15]([S:20]([NH2:23])(=[O:22])=[O:21])[CH:16]=[CH:17][C:18]=1F.Cl>O1CCCC1.ClCCl.CN(C)C=O>[Cl:12][C:13]1[CH:14]=[C:15]([S:20]([NH2:23])(=[O:21])=[O:22])[CH:16]=[CH:17][C:18]=1[O:9][CH2:8][C:2]1([F:1])[CH2:7][CH2:6][O:5][CH2:4][CH2:3]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 75098833-Chloro-4-fluorobenzenesulfonamideHCID 56971676(4-Fluorooxan-4-yl)methanol

Product 1

HCID 671267243-Chloro-4-((4-fluorotetrahydro-2h-pyran-4-yl)methoxy)benzenesulfonamide

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of EXAMPLE 296C (0.175 g) in tetrahydrofuran (5 ml) was added sodium hydride (0.209 g) and the reaction stirred at room temperature for 15 minutes. 3-Chloro-4-fluorobenzenesulfonamide (0.273 g) was added and the reaction stirred for 3 hours. To the thick suspension was added tetrahydrofuran (2 ml) and N,N-dimethylformamide (3 ml). The reaction was stirred for 3 hours at 60° C. then poured into dichloromethane (50 ml) and 1N aqueous HCl (50 ml). The organic layer was washed with brine (35 ml) dried over magnesium sulfate, filtered, and concentrated. Silica gel chromatography (Reveleris 40 g) eluting with a gradient of 10-100% ethyl acetate/hexanes over 30 minutes (flow=40 ml/minute) gave the title compound.

Workup

  1. stirringthe reaction stirred for 3 hours
  2. stirringThe reaction was stirred for 3 hours at 60° C.
  3. washThe organic layer was washed with brine (35 ml)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. washSilica gel chromatography (Reveleris 40 g) eluting with a gradient of 10-100% ethyl acetate/hexanes over 30 minutes (flow=40 ml/minute)

Sources & evidence

ORD record
ord-111b884ac67e4815be16f0e39385c8cd
Source dataset
uspto-grants-2015_05
Patent number
US09029404B2

Reaction notes

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