Triethylamine → tert-butyl N-[(4-amino-2-fluorophenyl)methyl]carbamate

HRID 272785Notes

Reaction equation

HRID 272785 reaction equation
[F:1][C:2]1[CH:9]=[C:8]([N+:10]([O-])=O)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[C:13]([O:17][C:18](ON=C(C1C=CC=CC=1)C#N)=[O:19])([CH3:16])([CH3:15])[CH3:14].C(N(CC)CC)C>CO.Cl.[Pd].ClCCl>[C:13]([O:17][C:18](=[O:19])[NH:5][CH2:4][C:3]1[CH:6]=[CH:7][C:8]([NH2:10])=[CH:9][C:2]=1[F:1])([CH3:16])([CH3:15])[CH3:14]

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 938652-(tert-Butoxycarbonyloxyimino)-2-phenylacetonitrileHCID 27590482-Fluoro-4-nitrobenzonitrile

Product 1

HCID 53439197tert-butyl N-[(4-amino-2-fluorophenyl)methyl]carbamate

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 313Hydrochloric AcidSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 2-fluoro-4-nitrobenzonitrile (0.541 g, 2.43 mmol) in methanol (20 mL) and hydrochloric acid (3 mL, 6 N) was hydrogenated (55 psi) over 10% palladium on carbon (164 mg) overnight. The reaction mixture was filtered and concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (5 mL) and treated with 2-(tert-butoxycarbonyloxyimino)-2-phenylacetonitrile (0.517 mg, 2.10 mmol) and triethylamine (0.6 mL, 4.3 mmol). After 16 h at rt, the reaction mixture was diluted with dichloromethane and washed with sodium bicarbonate solution and brine, dried (MgSO4), and concentrated under reduced pressure. The residue was purified by silica gel chromatography (gradient from 0 to 50% ethyl acetate in hexanes) to give 1-63A-(0.287 g, 60%) as a colorless oil which solidified on standing.

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe residue was dissolved in tetrahydrofuran (5 mL)
  4. washwashed with sodium bicarbonate solution and brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography (gradient from 0 to 50% ethyl acetate in hexanes)
  8. customto give 1-63A-(0.287 g, 60%) as a colorless oil which

Sources & evidence

ORD record
ord-1be4b4a69b3a46afad622859b35fa6d1
Source dataset
uspto-grants-2008_11
Patent number
US07456195B2

Reaction notes

Loading…