Sodium hydride → 2-Chlorobenzenesulfonic acid 3-[[N-(tert-butoxycarbonyl)piperidin-4-yl]methoxy]phenyl ester

HRID 482081

Reaction equation

HRID 482081 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([O:8][S:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[Cl:18])(=[O:11])=[O:10])[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].CS(O[CH2:26][CH:27]1[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]1)(=O)=O>CN(C=O)C>[C:36]([O:35][C:33]([N:30]1[CH2:31][CH2:32][CH:27]([CH2:26][O:1][C:2]2[CH:3]=[C:4]([O:8][S:9]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[Cl:18])(=[O:11])=[O:10])[CH:5]=[CH:6][CH:7]=2)[CH2:28][CH2:29]1)=[O:34])([CH3:39])([CH3:37])[CH3:38]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2765838Tert-butyl 4-(methylsulfonyloxymethyl)piperidine-1-carboxylateHCID 540152812-Chlorobenzenesulfonic acid 3-hydroxyphenyl ester

Product 1

HCID 537395992-Chlorobenzenesulfonic acid 3-[[N-(tert-butoxycarbonyl)piperidin-4-yl]methoxy]phenyl esterYield 69%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-chlorobenzenesulfonic acid 3-hydroxyphenyl ester (285 mg, 1.0 mmol), as prepared in step d, in DMF (5 mL) was added NaH (95%, 26 mg, 1.1 mmol). The reaction was stirred under nitrogen for 10 min. N-(tert-Butoxycarbonyl)-4-piperidinemethanol methanesulfonate (293 mg, 1.0 mmol), as prepared in the preceding step, was added and the reaction mixture was stirred at 50° C. under nitrogen for 3 h. The reaction mixture was then partitioned between water (50 mL) and ethyl acetate (150 mL). The organic phase was washed sequentially with saturated NaHCO3 (2×50 mL) and brine (2×50 mL), dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash column chromatography (2:1 hexane:ethyl acetate) to give the title compound as a colorless syrup (325 mg, 69%). 1H-NMR (300 MHz, CDCl3) δ 1.26 (m, 2H), 1.47 (s, 9H), 1.78 (d, 2H), 1.91 (m, 1H), 2.74 (t, 2H), 3.72 (d, 2H), 4.13 (m, 2H), 6.69 (m, 2H), 6.76 (dd, 1H), 7.16 (m, 1H), 7.37 (t, 1H), 7.62 (m, 2H), 7.95 (dd, 1H).

Workup

  1. additionwas added
  2. stirringthe reaction mixture was stirred at 50° C. under nitrogen for 3 h
  3. customThe reaction mixture was then partitioned between water (50 mL) and ethyl acetate (150 mL)
  4. washThe organic phase was washed sequentially with saturated NaHCO3 (2×50 mL) and brine (2×50 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography (2:1 hexane:ethyl acetate)

Sources & evidence

ORD record
ord-706b093e546f4f0db12fcc466bd6d130
Source dataset
uspto-grants-1998_08
Patent number
US05792769

Linked notes

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