Hydrochloric Acid → HCID 86639351, compound

HRID 1626052Notes

Reaction equation

HRID 1626052 reaction equation
[C:1]([O:8][CH3:9])(=[O:7])/[CH:2]=[CH:3]/[C:4]([OH:6])=[O:5].C(OC([N:17]1[CH2:22][CH2:21][N:20]([C:23](=[O:26])[CH2:24][Cl:25])[CH2:19][CH2:18]1)=O)(C)(C)C.C(=O)([O-])O.[Cs+].Cl>CN1C(=O)CCC1.O1CCOCC1>[ClH:25].[C:1]([O:8][CH3:9])(=[O:7])/[CH:2]=[CH:3]/[C:4]([O:6][CH2:24][C:23](=[O:26])[N:20]1[CH2:19][CH2:18][NH:17][CH2:22][CH2:21]1)=[O:5]

Participants

7

Reactant 4

HCID 313Hydrochloric Acid2×HCID 2734983Cesium bicarbonateHCID 5369209Monomethyl FumarateHCID 15829156Tert-butyl 4-(2-chloroacetyl)piperazine-1-carboxylate

Product 1

HCID 86639351HCID 86639351, compoundYield 41.4%

Reagents, catalysts & solvents 2

HCID 13387N-methyl-2-pyrrolidoneSolventHCID 312751,4-DioxaneSolvent

Procedure

Following general procedure A, methyl hydrogen fumarate (MHF) (1.00 g, 7.68 mmol) dissolved in NMP was reacted at ca. 55° C. with 1-(tert-butyloxycarbonyl)-4-chloroacetyl piperazine (2.42 g, 9.22 mmol) in the presence of CsHCO3 (1.78 g, 9.22 mmol). After work-up and removal of the solvent, the crude material was obtained as a white solid. The solid was reacted at room temperature with 15 mL of a 4 molar (4 M) solution of hydrogen chloride (HCl) in 1,4-dioxane. After removal of the solvents, the solid hydrochloride salt was further purified by mass-guided preparative HPLC to provide 0.93 g (41% yield) of the title compound (14) as a white solid after lyophilization of the solvents in the presence of an excess of aqueous 1 normal (1 N) hydrochloric acid. 1H NMR (D2O, 400 MHz): δ 6.93-6.86 (m, 2H), 4.92 (s, 2H), 3.70-3.63 (m, 7H), 3.23 (t, J=5.2 Hz, 2H), 3.17 (t, J=6 Hz, 2H). MS (ESI): m/z 257.13 (M+H)+.

Workup

  1. customAfter work-up and removal of the solvent
  2. customthe crude material was obtained as a white solid
  3. customAfter removal of the solvents
  4. customthe solid hydrochloride salt was further purified by mass-guided preparative HPLC

Sources & evidence

ORD record
ord-08202e0175b4452889d242b76f7f8d27
Source dataset
uspto-grants-2014_07
Patent number
US08785443B2

Reaction notes

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