Ammonia → HCID 57474465, compound

HRID 2043528Notes

Reaction equation

HRID 2043528 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[CH:7]2)([O-:3])=[O:2].[F:13][CH:14]1[C:19](=O)[CH2:18][CH2:17][N:16](C(OC(C)(C)C)=O)[CH2:15]1.N>C(O)(=O)C.OP(O)(O)=O>[F:13][CH:14]1[C:19]([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:18][CH2:17][NH:16][CH2:15]1

Participants

6

Reactant 3

HCID 222AmmoniaHCID 225235-NitroindoleHCID 10560711TERT-BUTYL 3-FLUORO-4-OXOPIPERIDINE-1-CARBOXYLATE

Product 1

HCID 57474465HCID 57474465, compoundYield 47%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolvent3×HCID 1004Phosphoric AcidSolvent

Procedure

A solution of 5-nitroindole (38) (1.0 g, 6.167 mmol) in glacial acetic acid (10 mL) at 90° C. was treated with compound 130 (1.33 g, 6.167 mmol) in glacial AcOH (5 mL), 1 M H3PO4 in glacial AcOH (5 mL) and the resulting solution was stirred at same temperature for 16 h. The reaction was brought to room temperature, poured into 15% cold aqueous ammonia solution (100 mL) and product was extracted into ethyl acetate (2×50 mL). The combined ethyl acetate layer was washed with brine (25 mL) and dried (Na2SO4). Solvent was evaporated and crude was purified by column chromatography (2 M NH3 in methanol: CH2Cl2, 1:99 to 5:95) to obtain compound 131 (0.75 g, 47%) as a yellow solid. mp 205-207° C.; 1H NMR (DMSO-d6) δ 2.35 (brs, 1H), 2.86-3.06 (m, 1H), 3.19-3.26 (m, 1H), 3.35-3.58 (m, 2H), 5.28 (d, 1H, J=49.5 Hz), 6.53-6.56 (m, 1H), 7.58 (d, 1H, J=8.7 Hz), 7.74 (s, 1H), 8.02 (dd, 1H, J=2.4, 9.0 Hz), 8.68 (d, 1H, J=2.4 Hz), 11.94 (s, 1H); ESI-MS m/z (%): 262 (MH+, 100), 233 (50).

Workup

  1. customwas brought to room temperature
  2. extractionwas extracted into ethyl acetate (2×50 mL)
  3. washThe combined ethyl acetate layer was washed with brine (25 mL)
  4. dry with materialdried (Na2SO4)
  5. customSolvent was evaporated
  6. customcrude was purified by column chromatography (2 M NH3 in methanol: CH2Cl2, 1:99 to 5:95)

Sources & evidence

ORD record
ord-e9404c8f44b2460c92d7f292dc48b337
Source dataset
uspto-grants-2013_11
Patent number
US08586620B2

Reaction notes

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