Ammonium formate → Cyclohexylmethyl (2-amino-5-(thiophen-2-yl)phenyl)carbamate

HRID 2201682Notes

Reaction equation

HRID 2201682 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[S:11][CH:12]=[CH:13][CH:14]=2)=[CH:6][C:5]=1[NH:15][C:16](=[O:25])[O:17][CH2:18][CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1)([O-])=O.C([O-])=O.[NH4+]>CO.C1COCC1.[Zn]>[NH2:1][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[S:11][CH:12]=[CH:13][CH:14]=2)=[CH:6][C:5]=1[NH:15][C:16](=[O:25])[O:17][CH2:18][CH:19]1[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]1

Participants

6

Reactant 2

HCID 2723923Ammonium formateHCID 71007336Cyclohexylmethyl (2-nitro-5-(thiophen-2-yl)phenyl)carbamate

Product 1

HCID 71465703Cyclohexylmethyl (2-amino-5-(thiophen-2-yl)phenyl)carbamateYield 100%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of cyclohexylmethyl (2-nitro-5-(thiophen-2-yl)phenyl)carbamate (0.09 g, 0.25 mmol, 1.0 equiv.) in methanol (5 mL) and THF (5 mL) were added Zn (0.08 mg, 1.25 mmol, 5.0 equiv.) and HCOONH4 (0.13 mmol, 2.0 mmol, 8.0 equiv.) at room temperature. The reaction mixture was stirred at room temperature for 4 h then filtered through celite and concentrated under reduced pressure. The crude residue was diluted with ethyl acetate, washed with water and brine. The combined organic layers were dried over sodium sulfate, filtered and concentrated. The crude residue was purified by column chromatography (silica gel, 30% EtOAc/hexanes) to afford cyclohexylmethyl (2-amino-5-(thiophen-2-yl)phenyl)carbamate (0.08 g, 100% yield). ESI+ MS: m/z 331 ([M+H]+), 1H NMR (500 MHz, d6-DMSO): δ 8.58 (bs, 1H), 7.52 (bs, 1H), 7.33 (d, J=4.5 Hz, 1H), 7.22-7.14 (m, 2H), 7.03 (dd, J=3.5, 5.0 Hz, 1H), 6.72 (d, J=8.0 Hz, 1H), 5.11 (s, 2H), 3.89 (d, J=6.5 Hz, 2H), 1.80-1.38 (m, 6H), 1.25-1.03 (m, 3H), 1.03-0.92 (m, 2H).

Workup

  1. filtrationthen filtered through celite and
  2. concentrationconcentrated under reduced pressure
  3. additionThe crude residue was diluted with ethyl acetate
  4. washwashed with water and brine
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude residue was purified by column chromatography (silica gel, 30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-9c92793fada4485a99cb4b3c8ccda380
Source dataset
uspto-grants-2016_06
Patent number
US09365498B2

Reaction notes

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