Acetic Acid → HCID 11952002, compound

HRID 1669075Notes

Reaction equation

HRID 1669075 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[O-:7][N+:8]1[C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][C:12]=2[N:11]=[C:10]([CH2:21][CH2:22][CH:23]=O)[N:9]=1)[CH2:18][CH2:17][CH2:16]3.[BH3-]C#N.[Na+].CC(O)=O>CO>[N:1]1([CH2:23][CH2:22][CH2:21][C:10]2[N:9]=[N+:8]([O-:7])[C:13]3[CH:14]=[C:15]4[C:19]([CH2:18][CH2:17][CH2:16]4)=[CH:20][C:12]=3[N:11]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8082PiperidineHCID 5003444Sodium cyanoborohydrideHCID 57786560HCID 57786560, compound

Product 1

HCID 11952002HCID 11952002, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Piperidine (3.0 g, 35 mmol) was added to a stirred solution of propanal 75 (1.5 g, 6.2 mmol) in MeOH (100 mL) at 0° C. and the solution stirred for 30 min. NaCNBH3 (1.5 g, 24 mmol) was added and the solution stirred at 0° C. for 30 min and then HOAc (2 mL) was added and the mixture was stirred at 20° C. for 16 h. The solvent was evaporated and the residue was partitioned between DCM (200 mL) and water (200 mL). The aqueous phase was extracted with DCM (2×200 mL), the combined organic phase was dried and the solvent evaporated. The residue was purified by chromatography, eluting with 10% MeOH/EtOAc, to give 1-oxide 86 (1.33 g, 69%) as a yellow oil: 1H NMR δ 8.24 (s, 1H, H-9), 7.74 (s, 1H, H-5), 3.09-3.15 (m, 4H, H-6, H-8), 3.02-3.07 (m, 2H, CH2), 2.82-2.95 (m, 6H, 3×CH2), 2.27-2.38 (m, 2H, CH2), 2.17-2.26 (m, 2H, H-7), 1.76-1.87 (m, 4H, 2×CH2), 1.50-1.60 (m, 2H, CH2); 13C NMR δ 164.3, 155.0, 149.2, 147.4, 132.3, 122.7, 114.2, 57.1, 53.5 (2), 34.3, 33.2, 32.8, 25.7 (2), 23.7, 22.9, 22.6; HRMS (FAB+) calcd for C18H25N4O (MH+) m/z 313.2025, found 313.2025.

Workup

  1. stirringthe solution stirred at 0° C. for 30 min
  2. stirringthe mixture was stirred at 20° C. for 16 h
  3. customThe solvent was evaporated
  4. customthe residue was partitioned between DCM (200 mL) and water (200 mL)
  5. extractionThe aqueous phase was extracted with DCM (2×200 mL)
  6. customthe combined organic phase was dried
  7. customthe solvent evaporated
  8. customThe residue was purified by chromatography
  9. washeluting with 10% MeOH/EtOAc

Sources & evidence

ORD record
ord-a4f4114c369046a3af5a2a7a6ca6cc4c
Source dataset
uspto-grants-2011_08
Patent number
US07989451B2

Reaction notes

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