Dimethylformamide → HCID 86637185, compound

HRID 1854451Notes

Reaction equation

HRID 1854451 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([CH3:17])[CH:13]([C:18]([OH:20])=O)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(=O)C([Cl:24])=O.CN(C=O)C>C(Cl)Cl>[Cl:24][C:18]([CH:13]1[CH:14]([CH3:17])[CH2:15][CH2:16][N:11]([C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:10])[CH2:12]1)=[O:20]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 58009930HCID 58009930, compound

Product 1

HCID 86637185HCID 86637185, compoundYield 101.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-(benzyloxycarbonyl)-4-methylpiperidine-3-carboxylic acid (1.28 g, 4.62 mmol) in DCM (40 mL) was added oxalyl chloride (0.930 mL, 10.6 mmol) followed by the drop-wise addition of DMF (0.072 mL, 0.92 mmol). The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated to yield crude benzyl 3-(chlorocarbonyl)-4-methylpiperidine-1-carboxylate (1.4 g, 4.7 mmol) which was dissolved in a mixture of Et2O and MeCN (1:1, 16 mL) and added to a solution of trimethylsilyldiazomethane (2 M in Et2O, 9.47 mL, 18.5 mmol) in Et2O and MeCN (1:1, 16 mL) that was cooled to about 0° C. The resulting mixture was stirred at about 0° C. for about 4 h and quenched by a drop-wise addition of 48% aqueous HBr. The organic solvents were removed and the residue was purified by silica gel chromatography eluting with a gradient of 10-40% EtOAc in heptane. The product-containing fractions were concentrated under reduced pressure to give benzyl 3-(2-bromoacetyl)-4-methylpiperidine-1-carboxylate (0.78 g, 47%): LC/MS (Table 2, Method a) Rt=2.50 min; MS m/z: 356 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated

Sources & evidence

ORD record
ord-4f1a6b8fe4b540088af0dbd2fbe3a04e
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

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