Sodium Iodide → 2,2-dimethylpropionic acid 2-((S)-3-tert-butoxycarbonylaminopiperidin-1-yl)ethyl ester

HRID 243031Notes

Reaction equation

HRID 243031 reaction equation
Br[CH2:2][CH2:3][O:4][C:5](=[O:10])[C:6]([CH3:9])([CH3:8])[CH3:7].[C:11]([O:15][C:16](=[O:24])[NH:17][C@H:18]1[CH2:23][CH2:22][CH2:21][NH:20][CH2:19]1)([CH3:14])([CH3:13])[CH3:12].C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>CN(C=O)C>[C:11]([O:15][C:16]([NH:17][C@H:18]1[CH2:23][CH2:22][CH2:21][N:20]([CH2:2][CH2:3][O:4][C:5](=[O:10])[C:6]([CH3:9])([CH3:8])[CH3:7])[CH2:19]1)=[O:24])([CH3:14])([CH3:12])[CH3:13]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 1514171tert-butyl N-[(3S)-piperidin-3-yl]carbamateHCID 145722042-Bromoethyl 2,2-dimethylpropanoate

Product 1

HCID 681570962,2-dimethylpropionic acid 2-((S)-3-tert-butoxycarbonylaminopiperidin-1-yl)ethyl esterYield 98.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 2,2-dimethylpropionic acid 2-bromoethyl ester (2.3 g, 11 mmol), (5)-piperidin-3-ylcarbamic acid tert-butyl ester (2 g, 10.0 mmol), potassium carbonate (4.15 g, 30 mmol) and sodium iodide (0.15 g, 1 mmol) in DMF (20 mL) was stirred at RT for 3 days. The reaction mixture was partitioned between water and EtOAc. The aqueous phase was extracted with EtOAc and the combined organic fractions were washed with water, followed by brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, eluant 10-40% EtOAc in cyclohexane) affording the title compound as a colourless oil (3.23 g, 98%). 1H NMR (CDCl3, 300 MHz): 5.08 (1H, bs), 4.27-4.07 (2H, m), 3.73 (1H, bs), 2.65-2.50 (3H, m), 2.48 (1H, bs), 2.30-2.24 (1H, m), 1.74-1.61 (1H, m), 1.58-1.47 (3H, m), 1.44 (9H, s), 1.21 (9H, s).

Workup

  1. customThe reaction mixture was partitioned between water and EtOAc
  2. extractionThe aqueous phase was extracted with EtOAc
  3. washthe combined organic fractions were washed with water
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by column chromatography (Si—PCC, eluant 10-40% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-55f02ade2fed43f689698b9a9378c547
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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