Acetic Acid → N-Ethyl-4-(5-nitro-1H-indol-3-yl)cyclohex-3-enamine

HRID 2043523Notes

Reaction equation

HRID 2043523 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[C:7]2[C:13]1[CH2:18][CH2:17][C:16](=O)[CH2:15][CH:14]=1)([O-:3])=[O:2].Cl.[CH2:21]([NH2:23])[CH3:22].C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.[OH-].[Na+]>[CH2:21]([NH:23][CH:16]1[CH2:17][CH2:18][C:13]([C:7]2[C:6]3[C:10](=[CH:11][CH:12]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[NH:9][CH:8]=2)=[CH:14][CH2:15]1)[CH3:22]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 11198Ethylamine hydrochlorideHCID 5049666Sodium triacetoxyborohydrideHCID 573845384-(5-nitro-1H-indol-3-yl)cyclohex-3-en-1-one

Product 1

HCID 59715785N-Ethyl-4-(5-nitro-1H-indol-3-yl)cyclohex-3-enamineYield 97%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 14798Sodium HydroxideSolvent

Procedure

A solution of compound 79 (1.0 g, 3.902 mmol) in dry 1,2-dichloroethane (10 mL) was treated with ethylamine hydrochloride (0.31 g, 3.902 mmol), glacial acetic acid (0.22 mL, 3.902 mmol) and NaBH(OAc)3 (1.24 g, 5.853 mmol) at room temperature and the resulting mixture was stirred for overnight (14 h). The reaction was diluted with 1 N NaOH (30 mL) and product was extracted into ethyl acetate (2×50 mL). The combined ethyl acetate layer was washed with brine (20 mL) and dried (Na2SO4). Solvent was evaporated and crude was purified by column chromatography (2 M NH3 in methanol: CH2Cl2, 1:9) to obtain compound 117 (1.08 g, 97%) as a dark yellow solid. mp 177-179° C.; 1H NMR (DMSO-d6) δ: 1.03 (t, 3H, J=6.9 Hz), 1.39-1.52 (m, 2H), 1.94-2.00 (m, 2H), 2.40-2.80 (m, 3H), 3.16 (s, 2H), 4.07 (brs, 1H), 6.13 (s, 1H), 7.54 (d, 1H, J=9.0 Hz), 7.62 (s, 1H), 8.00 (dd, 1H, J=2.4, 9.0 Hz), 8.67 (d, 1H, J=2.4 Hz), 11.83 (brs, 1H); ESI-MS m/z (%): 286 (MH+, 100).

Workup

  1. extractionwas extracted into ethyl acetate (2×50 mL)
  2. washThe combined ethyl acetate layer was washed with brine (20 mL)
  3. dry with materialdried (Na2SO4)
  4. customSolvent was evaporated
  5. customcrude was purified by column chromatography (2 M NH3 in methanol: CH2Cl2, 1:9)

Sources & evidence

ORD record
ord-a829c21839c242928ee0e2b5f17918d9
Source dataset
uspto-grants-2013_11
Patent number
US08586620B2

Reaction notes

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