Triethylamine → tert-butyl (3S)-3-methyl-4-(pyridin-2-ylmethyl)piperazine-1-carboxylate

HRID 1804634Notes

Reaction equation

HRID 1804634 reaction equation
[CH3:1][C@H:2]1[CH2:7][N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:5][CH2:4][NH:3]1.Br.Br[CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=1.C(N(CC)CC)C>C1COCC1>[CH3:1][C@@H:2]1[N:3]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)[CH2:4][CH2:5][N:6]([C:8]([O:10][C:11]([CH3:13])([CH3:12])[CH3:14])=[O:9])[CH2:7]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27347202-(Bromomethyl)pyridine hydrobromideHCID 7023035(S)-1-Boc-3-methylpiperazine

Product 1

HCID 67986528tert-butyl (3S)-3-methyl-4-(pyridin-2-ylmethyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of (S)-2-methyl-4-N—BOC-piperazine (400 mg, 1.997 mmol) and 2-(bromomethyl)pyridine hydrobromide (505 mg, 1.997 mmol) in anhydrous THF (5 ml) was added triethylamine (0.7 ml, 4.99 mmol) and the resulting mixture stirred at RT for 3 days. The mixture partitioned between water and EtOAc; organic layer washed with sat. NaCl, dried over MgSO4, filtered and evaporated. The residue purified by column chromatography (eluent: 5% MeOH in DCM) to give 320 mg (55%) to afford the title compound as a yellow oil. 1H NMR (CDCl3): 1.14 (d, J 6.2 Hz, 3H), 1.47 (s, 9H), 2.25 (t, J 9.5 Hz, 1H), 2.51 (m, 1H), 2.70 (d, J 11.6 Hz, 1H), 2.84 (brs, 1H), 3.15 (t, J 10.1, 1H), 3.47 (d, J 14.2 Hz, 1H), 3.69 (d, J 13.0 Hz, 1H), 3.75 (brs, 1H), 4.08 (d, J 14.0, 1H), 7.17 (dd, J 7.1 and 5.3, 1H), 7.45 (d, J 7.8, 1H), 7.66 (m, 1H), 8.56 (d, J=4.7 Hz, 1H).

Workup

  1. customThe mixture partitioned between water and EtOAc
  2. washorganic layer washed with sat. NaCl
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue purified by column chromatography (eluent: 5% MeOH in DCM)
  7. customto give 320 mg (55%)

Sources & evidence

ORD record
ord-02f16057123244a994ca5a27a7231190
Source dataset
uspto-grants-2013_01
Patent number
US08354403B2

Reaction notes

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