Acetic Acid → 1-Cyclopropyl-4-(4-nitrophenyl)piperidine

HRID 1050536Notes

Reaction equation

HRID 1050536 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].[BH3-][C:17]#N.[Na+].[CH3:20][C:21](O)=O>CO>[CH:21]1([N:13]2[CH2:12][CH2:11][CH:10]([C:7]3[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=3)[CH2:15][CH2:14]2)[CH2:20][CH2:17]1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 159258174-(4-Nitrophenyl)piperidine

Product 1

HCID 686721561-Cyclopropyl-4-(4-nitrophenyl)piperidine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

4-(4-Nitrophenyl)piperidine (1.00 g, 4.85 mmol) was dissolved in 80 mL MeOH and 2 mL HOAc. To it was added (1-ethoxycycloproxy)trimethylsilane, and the mixture was stirred at RT for 40 min To it was then added NaBH3CN (1.83 g, 29.0 mmol), and the mixture was stirred in 65° C. bath for overnight. It was concentrated in vacuo to dryness, diluted with 120 mL EtOAc, washed with 1N NaOH and water ×2, dried, concentrated in vacuo, and subjected to silica flash column using 0 to 4% MeOh in DCM to isolate 1-cyclopropyl-4-(4-nitrophenyl)piperidine (256). It was dissolved in 50 mL EtOAc. To it was added 10% Pd/C (0.5 g), and the mixture was hydrogenated using a H2 balloon at RT for overnight. The mixture was filtered through celite, and concentrated in vacuo to give 4-(1-cyclopropylpiperidin-4-yl)aniline (257) (960 mg, 91% overall) as a white solid.

Workup

  1. concentrationIt was concentrated in vacuo to dryness
  2. additiondiluted with 120 mL EtOAc
  3. washwashed with 1N NaOH and water ×2
  4. customdried
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-08fcf1a5f2f2485280f820a635e5a63d
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

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