Pyridine → Tert-butyl 4-(3-(dimethylcarbamoyloxy)phenylcarbamoyl)-4-(methoxymethyl)piperidine-1-carboxylate

HRID 216060Notes

Reaction equation

HRID 216060 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH2:17][O:18][CH3:19])([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].N1C=CC=CC=1.C(Cl)(=O)C(Cl)=O.[CH3:32][N:33]([CH3:44])[C:34](=[O:43])[O:35][C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([NH2:42])[CH:37]=1>CN(C=O)C.C(Cl)Cl.C(OCC)(=O)C>[CH3:32][N:33]([CH3:44])[C:34]([O:35][C:36]1[CH:37]=[C:38]([NH:42][C:14]([C:11]2([CH2:17][O:18][CH3:19])[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:12]2)=[O:16])[CH:39]=[CH:40][CH:41]=1)=[O:43]

Participants

8

Reactant 4

HCID 1049PyridineHCID 298773-Aminophenyl dimethylcarbamateHCID 65578Oxalyl chlorideHCID 218825761-((Tert-butoxy)carbonyl)-4-(methoxymethyl)piperidine-4-carboxylic acid

Product 1

HCID 67037885Tert-butyl 4-(3-(dimethylcarbamoyloxy)phenylcarbamoyl)-4-(methoxymethyl)piperidine-1-carboxylateYield 90%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1-(tert-butoxycarbonyl)-4-(methoxymethyl)-piperidine-4-carboxylic acid from step B (718 mg, 2.63 mmol), pyridine (0.84 mL, 10.52 mmol), and DMF (catalytic, 3 drops) in CH2Cl2 (13 mL) was added dropwise oxalyl chloride (0.25 mL, 2.89 mmol, caution: exothermic). After gas evolution subsided, the reaction was stirred at ambient temperature for 30 minutes. 3-Aminophenyl dimethylcarbamate (475 mg, 2.63 mmol) was added in one portion to this solution and stirred for another 30 minutes. The reaction was quenched with saturated aqueous NH4Cl, and the aqueous layer was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated under vacuum. Silica gel chromatography (50% ethyl acetate:hexanes) afforded the title compound (1.03 g, 90% yield for two steps). MS (ES+) [M+NH4]+=453.3

Workup

  1. stirringstirred for another 30 minutes
  2. customThe reaction was quenched with saturated aqueous NH4Cl
  3. extractionthe aqueous layer was extracted with ethyl acetate (3×50 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-5c25f9b1b6944ba69aa640a29dd05064
Source dataset
uspto-grants-2012_06
Patent number
US08193202B2

Reaction notes

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