Ammonia → (2R,4R)-1-tert-butyl 2-methyl 4-(3-(4-cyanophenyl)ureido)piperidine-1,2-dicarboxylate

HRID 1971306Notes

Reaction equation

HRID 1971306 reaction equation
[N:1]([C:4]1[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[CH:6][CH:5]=1)=[C:2]=[O:3].[NH2:12][C@@H:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[C@@H:15]([C:26]([O:28][CH3:29])=[O:27])[CH2:14]1.CCN(CC)CC.N>C1COCC1.CO>[C:8]([C:7]1[CH:10]=[CH:11][C:4]([NH:1][C:2](=[O:3])[NH:12][C@@H:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:20])[C@@H:15]([C:26]([O:28][CH3:29])=[O:27])[CH2:14]2)=[CH:5][CH:6]=1)#[N:9]

Participants

7

Reactant 4

HCID 222AmmoniaHCID 8471TriethylamineHCID 1703804-Cyanophenyl isocyanateHCID 54209755(2R,4R)-1-tert-butyl 2-methyl 4-aminopiperidine-1,2-dicarboxylate

Product 1

HCID 57539094(2R,4R)-1-tert-butyl 2-methyl 4-(3-(4-cyanophenyl)ureido)piperidine-1,2-dicarboxylateYield 93.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-isocyanatobenzonitrile (1.17 g, 8.13 mmol) was added to a solution of (2R,4R)-1-tert-butyl 2-methyl 4-aminopiperidine-1,2-dicarboxylate (2.0 g, 7.7 mmol) and NEt3 (1.3 mL, 9.3 mmol) in THF (30 mL), and the resulting solution was stirred at room temperature for 6 hours. 1M ammonia in methanol (5 mL) was added to reaction mixture to quench excess isocyanine. Water (100 mL) and ethyl acetate (200 mL) were added to the mixture. The organic layer was separated and dried over MgSO4 and concentrated to give a solid. Purification was done by Companion (ReadySep, 80 g, silica gel packed) with ethyl acetate/heptane from 40-70% to give the urea as a white solid 2.9 g (90%). LC-MS: 403.2, 401.3 (t=2.6 min).

Workup

  1. customto quench excess isocyanine
  2. additionWater (100 mL) and ethyl acetate (200 mL) were added to the mixture
  3. customThe organic layer was separated
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customto give a solid
  7. customPurification

Sources & evidence

ORD record
ord-163c62e754a840b18e03e0c89bcee111
Source dataset
uspto-grants-2013_04
Patent number
US08431597B2

Reaction notes

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