Cyclopropylamine → tert-Butyl 4-(cyclopropylcarbamoyl)piperidine-1-carboxylate

HRID 1804602Notes

Reaction equation

HRID 1804602 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:17]1([NH2:20])[CH2:19][CH2:18]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH:17]1([NH:20][C:14]([CH:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:12]2)=[O:16])[CH2:19][CH2:18]1

Participants

5

Reactant 3

HCID 69828CyclopropylamineHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 24688815tert-Butyl 4-(cyclopropylcarbamoyl)piperidine-1-carboxylateYield 89.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid (670 mg, 2.92 mmol) and cyclopropylamine (167 mg, 2.92 mmol) in 15 mL anhydrous DMF was added HATU (1.11 g, 2.92 mmol) and the resulting mixture stirred at RT under nitrogen atmosphere for 3 h. The mixture was washed with water and extracted with ethyl acetate (2×50 mL). The organics were washed with brine, separated, dried over sodium sulfate, filtered and concentrated under vacuum. The residue was purified by Biotage MPLC (silica gel 40+ column) eluting with 50% ethyl acetate in hexane to afford the product (704 mg, 89%). ESI-MS calculated for C14H24N2O3: Exact Mass: 268.18. Found 169.17 (M-Boc)+ and 291.15 (MNa)+.

Workup

  1. washThe mixture was washed with water
  2. extractionextracted with ethyl acetate (2×50 mL)
  3. washThe organics were washed with brine
  4. customseparated
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified by Biotage MPLC (silica gel 40+ column)
  9. washeluting with 50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-66cfcc4bf93b4bcbae3993fce5b767d1
Source dataset
uspto-grants-2013_01
Patent number
US08354403B2

Reaction notes

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