Sodium hydride → 1-Boc-4-(2-fluorophenyl)-4-piperidinecarboxylic acid methyl ester

HRID 391460Notes

Reaction equation

HRID 391460 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10][C:11]([O:13][CH3:14])=[O:12].Cl[CH2:16][CH2:17][N:18]([CH2:26][CH2:27]Cl)[C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22]>CN(C)C=O>[F:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1([C:11]([O:13][CH3:14])=[O:12])[CH2:27][CH2:26][N:18]([C:19]([O:20][C:21]([CH3:23])([CH3:22])[CH3:24])=[O:25])[CH2:17][CH2:16]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2733230Methyl 2-fluorophenylacetateHCID 11230235N-BOC-N,N-Bis(2-chloroethyl)amine

Product 1

HCID 497602321-Boc-4-(2-fluorophenyl)-4-piperidinecarboxylic acid methyl esterYield 17%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A flask was charged with sodium hydride (2.14 g, 89.2 mmol) and dimethylformamide (70 ml) at 0° C. under nitrogen. Methyl 2-(2-fluorophenyl)acetate (5 g, 29.7 mmol) was added to the flask, and after stirring for 25 min, tert-butyl bis(2-chloroethyl)carbamate (8.6 g, 35.6 mmol) was added. The reaction was allowed to warm to rt and stirred overnight. The reaction was quenched with a saturated solution of ammonium chloride and extracted with ethyl acetate (5×100 mL). The organics were collected, washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue was purified via silica gel chromatography (10/90→50/50 ethyl acetate/hexanes) to yield 1.7 g (17%) of the desired product. 1H-NMR (CDCl3, 400 MHz) δ ppm 7.29 (m, 1H), 7.24 (m, 1H), 7.12 (m, 1H), 7.00 (m, 1H), 3.86 (m, 2H), 3.67 (m, 3H), 3.22 (m, 2H), 2.37 (m, 2H), 1.96 (m, 2H), 1.44 (s, 9H). Mass spec.: 360.22 (MNa)+. LC tr=3.503 min (Phenomenex-Luna 4.6×50 mm S10, 10% MeOH/90% H2O/0.1% TFA→90% MeOH/10% H2O/0.1% TFA Gradient Time=4 min, Flow rate=4 mL/min)

Workup

  1. stirringstirred overnight
  2. customThe reaction was quenched with a saturated solution of ammonium chloride
  3. extractionextracted with ethyl acetate (5×100 mL)
  4. customThe organics were collected
  5. washwashed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified via silica gel chromatography (10/90→50/50 ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-f9aba976f601477fa9baed51b0e332f4
Source dataset
uspto-grants-2013_02
Patent number
US08383821B2

Reaction notes

Loading…