Triethylamine → tert-Butyl 4-(1-(pyridin-3-yl)ethyl)piperazine-1-carboxylate

HRID 416775

Reaction equation

HRID 416775 reaction equation
N1C=[CH:5][CH:4]=[CH:3][C:2]=1[CH:7]([N:9]1[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]1)[CH3:8].[N:22]1C=CC=C(C(O)C)[CH:23]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.C(N1CCNCC1)(OC(C)(C)C)=O>CS(C)=O.CCOC(C)=O.CO.C(Cl)Cl>[N:22]1[CH:5]=[CH:4][CH:3]=[C:2]([CH:7]([N:9]2[CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])[CH2:13][CH2:14]2)[CH3:8])[CH:23]=1

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 101192alpha-Methyl-3-pyridinemethanolHCID 143452tert-Butyl piperazine-1-carboxylateHCID 60137623tert-Butyl 4-(1-(pyridin-2-yl)ethyl)piperazine-1-carboxylate2×

Product 1

HCID 66622025tert-Butyl 4-(1-(pyridin-3-yl)ethyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolventHCID 21584119Ethylacetate methanolSolvent

Procedure

This was prepared using the same procedure as for tert-butyl 4-(1-(pyridin-2-yl)ethyl)piperazine-1-carboxylate, but here using 1-(pyridin-3-yl)ethanol (J. Chem. Soc., Perkin Trans. 1, 2000, 4439-4444) (200 mg, 1.62 mmol), triethylamine (5.0 eq, 8.12 mmol, 1.13 mL), MsCl (2.0 eq, 3.25 mmol, 0.26 mL), CH2Cl2 (8 mL) at 0° C. for 30 minutes. A solution of ether-pentane (1:1, 20 mL) was added, the solid removed by filtration and the solvents removed in vacuo. The residue was then treated with N—BOC piperazine (4.0 eq, 6.50 mmol, 1.21 g) in DMSO (6 mL) at 60° C. for 18 h. Work up as described for tert-butyl 4-(1-(pyridin-2-yl)ethyl)piperazine-1-carboxylate, followed by column chromatography (EtOAc-MeOH, 95:5) gave the product (186 mg, 39% for two steps) as a colourless oil; 1H-NMR (500 MHz, CDCl3) 1.36 (d, J=6.8 Hz, 3H, CH3), 1.42 (s, 9H, C(CH3)3), 2.29-2.45 (m, 4H, piperazine N(CH2)2), 3.38 (t, J=5.0 Hz, 4H, piperazine N(CH2)2), 3.45 (q, J=6.8 Hz, 1H, CH), 7.23 (dd, br, J=7.9, 4.7 Hz, 1H, pyridine H-5), 7.64 (dt, J=7.8, 1.9 Hz, 1H, pyridine H-4), 8.47 (dd, J=4.8, 1.8 Hz, 1H, pyridine H-6), 8.52 (d, br, J=1.9 Hz, 1H, pyridine H-2);

Workup

  1. customThis was prepared
  2. customat 0° C.
  3. customfor 30 minutes
  4. customthe solid removed by filtration
  5. customthe solvents removed in vacuo
  6. customgave the product (186 mg, 39% for two steps) as a colourless oil

Sources & evidence

ORD record
ord-eb915e51ed0f4cb4b0239007b64ae9a0
Source dataset
uspto-grants-2012_01
Patent number
US08088761B2

Linked notes

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