Formic Acid → 4-(Isopropylamino)piperidine-4-carboxamide

HRID 1766985Notes

Reaction equation

HRID 1766985 reaction equation
C([N:8]1[CH2:13][CH2:12][C:11]([NH:17][CH:18]([CH3:20])[CH3:19])([C:14]([NH2:16])=[O:15])[CH2:10][CH2:9]1)C1C=CC=CC=1.C(O)=O>[Pd].CO>[C:14]([C:11]1([NH:17][CH:18]([CH3:20])[CH3:19])[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]1)(=[O:15])[NH2:16]

Participants

5

Reactant 2

HCID 284Formic AcidHCID 705731-Benzyl-4-(isopropylamino)piperidine-4-carboxamide

Product 1

HCID 967164-(Isopropylamino)piperidine-4-carboxamideYield 113.3%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A mixture of the 1-benzyl-4-isopropylamino-4-piperidinecarboxamide (250 mg, 0.91 mmol) (commercially available from Aldrich Chemical, Milwaukee, Wis.), 10% palladium on charcoal (30% by weight, 81 mg) and formic acid (5 mmol) in methanol (4 ml) was stirred vigorously overnight at room temperature. The reaction mixture was filtered through a celite pad and concentrated in vacuo to provide the product 4-carbamoyl-4-(isopropylamino)piperidine (191 mg, 90%) as a formic acid salt. A mixture of the chloride I-1f (100 mg, 0.28 mmol), 4-carbamoyl-4-(isopropylamino)-piperidine (85 mg, 0.306 mmol) and triethylamine (0.13 ml, 0.92 mmol) in dry ethanol (2 ml) was refluxed for 3 hrs. The reaction mixture was cooled to room temperature and water was added to precipitate out solids. The filtrate was acidified and washed with ethyl acetate to remove impurities. The aqueous layer was basified with 1 N NaOH and extracted with dichloromethane, dried and concentrated to give crude solid. This was combined with the filtered solids and purified using short plug silica gel with 10% MeOH:EtOAc as eluant to provide the desired product 1A-1 (46 mg, 30%) as a white solid: 1H NMR (400 MHz, CD3OD) δ 8.78 (s, 1H), 7.68–7.41 (m, 6H), 7.19–7.14 (t, 2H), 4.42 (br d, 2H), 4.16–4.13 (br t, 2H), 2.95–2.92 (m, 1H), 2.17–2.12 (m, 2H), 1.83–1.80 (br d, 2H), 1.10 (d, 6H); MS (m/z): 524.5 (M+H); Ret time (RT): 1.7 min.

Workup

  1. filtrationThe reaction mixture was filtered through a celite pad
  2. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b316bf4df97a48d9896544151f3bef78
Source dataset
uspto-grants-2007_06
Patent number
US07232823B2

Reaction notes

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