Triphenylphosphine → Benzenesulfonic acid 3-[[N-(tert-butoxycarbonyl)piperidin-4-yl]methoxy]-5-methylphenyl ester

HRID 482114Notes

Reaction equation

HRID 482114 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([O:9][S:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)(=[O:12])=[O:11])[CH:5]=[C:6]([CH3:8])[CH:7]=1.[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][CH:29]([CH2:32]O)[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1.C(Cl)Cl.O>[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][CH:29]([CH2:32][O:1][C:2]2[CH:3]=[C:4]([O:9][S:10]([C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)(=[O:12])=[O:11])[CH:5]=[C:6]([CH3:8])[CH:7]=2)[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:20])[CH3:21]

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylateHCID 11054545Benzenesulfonic acid 3-hydroxy-5-methylphenyl ester

Product 1

HCID 53954908Benzenesulfonic acid 3-[[N-(tert-butoxycarbonyl)piperidin-4-yl]methoxy]-5-methylphenyl esterYield 84.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of benzenesulfonic acid 3-hydroxy-5-methylphenyl ester (528 mg, 2.0 mmol), as prepared in the preceding step, N-(tert-butoxycarbonyl)-4-piperidinemethanol (430 mg, 2.0 mmol), as prepared in step f of Example 1, and triphenylphosphine (525 mg, 2.0 mmol) in tetrahydrofuran (20 mL) at 0° C. was added diethyl azodicarboxylate (349 mg, 2.0 mmol). The reaction mixture was stirred at 0° C. for 2 h and at room temperature for 3 h. The reaction mixture was diluted with methylene chloride (200 mL) and water (50 mL). The organic extract 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 (1:2 ethyl acetate:hexane) to give the title compound as a colorless liquid (781 mg, 84%). 1H-NMR (300 MHz, CDCl3) δ 1.24 (m, 2H), 1.47 (s, 9H), 1.76 (m, 2H), 1.88 (m, 1H), 2.24 (s, 3H), 2.73 (t, 2H), 3.66 (d, 2H), 4.12 (m, 2H), 6.32 (s, 1H), 6.58 (s, 1H), 7.54 (t, 2H), 7.67 (t, 1H), 7.86 (d, 2H).

Workup

  1. extractionThe organic extract
  2. washwas washed sequentially with saturated NaHCO3 (2×50 mL) and brine (2×50 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash column chromatography (1:2 ethyl acetate:hexane)

Sources & evidence

ORD record
ord-2ba927239ba44f37801179bb1b230877
Source dataset
uspto-grants-1998_08
Patent number
US05792769

Reaction notes

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