Tert-butyl 4-cyanophenylcarbamate → Tert-butyl N-(4-(aminomethyl)phenyl)carbamate

HRID 1191033Notes

Reaction equation

HRID 1191033 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>C1COCC1.C(O)(C)C.[Pd]>[C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:13][NH2:14])=[CH:15][CH:16]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 1

HCID 10130644Tert-butyl 4-cyanophenylcarbamate

Product 1

HCID 2794659Tert-butyl N-(4-(aminomethyl)phenyl)carbamateYield 36%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 22597222Tetrahydrofuran 2-propanolSolvent

Procedure

Add a solution of 4-(tert-butoxycarbonylamino)-benzonitrile (1 g, 4.58 mmol) in THF/iso-propanol (1:1, 142 mL) to 10% Pd/C (Degussa type E101, 0.56 g, 0.26 mmol) via syringe under N2. Purge the reaction mixture with nitrogen and submit the mixture to hydrogenation at 50 psi overnight. Filter the catalyst through Celite® and wash thoroughly with iso-propanol (100 mL) and THF (100 mL). Concentrate in vacuo and purify the crude mixture by chromatography on silica gel eluting with DCM/2M ammonia in methanol (1:0 to 95:5 gradient over 30 min; 95:5 over 3 min; 95:5 to 9:1 gradient over 30 min and 9:1 over 30 min) to obtain the desired intermediate (0.364 g, 36%). MS (ES−) m/z: 220.1 (M−2H)−.

Workup

  1. customPurge the reaction mixture with nitrogen
  2. customat 50 psi overnight
  3. filtrationFilter the catalyst through Celite®
  4. washwash thoroughly with iso-propanol (100 mL) and THF (100 mL)
  5. concentrationConcentrate in vacuo
  6. custompurify the crude mixture by chromatography on silica gel eluting with DCM/2M ammonia in methanol (1:0 to 95:5 gradient over 30 min; 95:5 over 3 min; 95:5 to 9:1 gradient over 30 min and 9:1 over 30 min)

Sources & evidence

ORD record
ord-b422fa9a063a46dda99a9947d3e0f552
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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