Citric Acid → (R)-tert-butyl 3-(tosyloxymethyl)piperidine-1-carboxylate

HRID 556697Notes

Reaction equation

HRID 556697 reaction equation
[OH:1][CH2:2][C@@H:3]1[CH2:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1.N1C=CC=CC=1.[C:22]1([CH3:32])[CH:27]=[CH:26][C:25]([S:28](Cl)(=[O:30])=[O:29])=[CH:24][CH:23]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1.O>[S:28]([O:1][CH2:2][C@@H:3]1[CH2:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1)([C:25]1[CH:26]=[CH:27][C:22]([CH3:32])=[CH:23][CH:24]=1)(=[O:30])=[O:29]

Participants

7

Reactant 4

HCID 311Citric AcidHCID 1049PyridineHCID 73974-Toluenesulfonyl chlorideHCID 1514447tert-butyl (3R)-3-(hydroxymethyl)piperidine-1-carboxylate

Product 1

HCID 11474148(R)-tert-butyl 3-(tosyloxymethyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of (R)-tert-butyl 3-(hydroxymethyl)piperidine-1-carboxylate (400 mg, 1.858 mmol) and pyridine (1.10 ml, 13.60 mmol) in tetrahydrofuran (5 ml) was added p-toluenesulfonyl chloride (425 mg, 2.230 mmol) and stirred for 10 hr. To the reaction was added citric acid (4 g) and water (10 mL) and extracted with ethyl acetate (3×10 mL). The organics were combined, dried (MgSO4), filtered, and concentrated. The residue was purified by Analogix® Intelliflash280™ (SiO2, 0-40% ethyl acetate in hexanes). 1H NMR (300 MHz, DMSO-d6) δ ppm 1.13-1.21 (m, 1H) 1.23-1.31 (m, 1H) 1.37 (s, 9H) 1.46-1.55 (m, 1H) 1.59-1.74 (m, 2H) 2.43 (s, 3H) 2.68-2.83 (m, 1H) 3.28-3.32 (m, 1H), 3.67-3.73 (m, 2H) 3.89 (d, J=6.10 Hz, 2H) 7.49 (m, 2H) 7.76-7.81 (m, 2H); MS (DCI) m/z 387 (M+NH4)+.

Workup

  1. extractionextracted with ethyl acetate (3×10 mL)
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by Analogix® Intelliflash280™ (SiO2, 0-40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-c8f9ff7999d448a89297acb032172166
Source dataset
uspto-grants-2011_11
Patent number
US08058293B2

Reaction notes

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