Triethylamine → Tert-butyl 4-[(5-chloro-2,3-dihydro-1-benzofuran-2-yl)carbonyl]piperazine-1-carboxylate

HRID 1772245Notes

Reaction equation

HRID 1772245 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][CH:8]([C:10]([OH:12])=O)[CH2:7][C:6]=2[CH:13]=1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.[N:43]1([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][CH:8]([C:10]([N:46]3[CH2:45][CH2:44][N:43]([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:48][CH2:47]3)=[O:12])[CH2:7][C:6]=2[CH:13]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 143452tert-Butyl piperazine-1-carboxylateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 31640255-Chloro-2,3-dihydro-benzofuran-2-carboxylic acid

Product 1

HCID 71900178Tert-butyl 4-[(5-chloro-2,3-dihydro-1-benzofuran-2-yl)carbonyl]piperazine-1-carboxylateYield 65.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-chloro-2,3-dihydro-1-benzofuran-2-carboxylic acid (1 g, 5 mmol) in N,N-dimethylformamide (10 ml) was added EDAC.HCl (1.45 g, 7.56 mmol, 1.5 eq), HOBt (1.02 g, 7.55 mmol, 1.5 eq), triethylamine (1.52 g, 15.0 mmol, 3 eq) and tert-butyl piperazine-1-carboxylate (935 mg, 5.02 mmol, 1 eq). The resulting solution was stirred overnight at room temperature, quenched with water (200 ml), and then extracted with ethyl acetate (3×200 ml). The combined organic layer was washed with brine (3×100 ml), dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The crude material was purified by silica gel chromatography using 10%-20% ethyl acetate in petroleum ether to elute. The product-containing fractions were combined and concentrated under vacuum to afford tert-butyl 4-[(5-chloro-2,3-dihydro-1-benzofuran-2-yl)carbonyl]piperazine-1-carboxylate as a off-white solid (1.2 g, 65%). (ES, m/z): [M+H]+ 367; 1H NMR (300 MHz, CDCl3): δ 7.05-7.22 (m, 2H), 6.72 (d, J=8.4 Hz, 1H), 5.38-5.45 (m, 1H), 3.75-3.90 (m, 3H), 3.25-3.70 (m, 7H), 1.50 (s, 9H).

Workup

  1. customquenched with water (200 ml)
  2. extractionextracted with ethyl acetate (3×200 ml)
  3. washThe combined organic layer was washed with brine (3×100 ml)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe crude material was purified by silica gel chromatography
  8. washto elute
  9. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-8aa3ba4f869e4e57a172dd4da2631abc
Source dataset
uspto-grants-2016_02
Patent number
US09249102B2

Reaction notes

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