Sodium hydride → HCID 66547112, compound

HRID 1841992Notes

Reaction equation

HRID 1841992 reaction equation
[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][C@@H:2]1[C:11]1[CH:31]=[CH:30][C:14]([CH2:15][N:16]2[CH2:21][CH2:20][CH:19]([NH:22][S:23]([CH2:26][CH2:27][CH2:28]Cl)(=[O:25])=[O:24])[CH2:18][CH2:17]2)=[CH:13][CH:12]=1.[H-].[Na+]>CN(C=O)C.CCOC(C)=O>[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][C@@H:2]1[C:11]1[CH:31]=[CH:30][C:14]([CH2:15][N:16]2[CH2:21][CH2:20][CH:19]([N:22]3[CH2:28][CH2:27][CH2:26][S:23]3(=[O:25])=[O:24])[CH2:18][CH2:17]2)=[CH:13][CH:12]=1

Participants

5

Reactant 2

HCID 24758Sodium hydrideHCID 68292779HCID 68292779, compound

Product 1

HCID 66547112HCID 66547112, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 3-chloro-propane-1-sulfonic acid {1-[(S)-4-(2,3-dihydro-benzo[1,4]dioxin-2-yl)-benzyl]-piperidin-4-yl}-amide (410 mg, 0.88 mmol) in DMF (5 mL) is added NaH (60% dispersion in mineral oil, 71 mg, 1.8 mmol). The reaction is heated to 80° C. for 1 h, diluted with EtOAc, washed with water and brine, dried over Na2SO4, filtered, and concentrated. The residue is purified by reversed phase HPLC eluting with a gradient of 0-80% MeCN in water (+0.1% TFA). The desired fractions are lyophilized, partitioned between saturated aqueous NaHCO3 and EtOAc. The organic layer is dried over Na2SO4, filtered and concentrated to provide the title compound (LC/MS method 1: ES+ m/z 429.4 [M+H]+, Rt=0.63 min)

Workup

  1. washwashed with water and brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue is purified by reversed phase HPLC
  6. washeluting with a gradient of 0-80% MeCN in water (+0.1% TFA)
  7. custompartitioned between saturated aqueous NaHCO3 and EtOAc
  8. dry with materialThe organic layer is dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-70d42e226c694888aa617bb38f99ae10
Source dataset
uspto-grants-2015_02
Patent number
US08946203B2

Reaction notes

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