Methylamine → HCID 69104936, compound

HRID 915819Notes

Reaction equation

HRID 915819 reaction equation
[Cl:1][C:2]1[CH:27]=[CH:26][C:5]([O:6][CH2:7][C:8]([N:10]2[CH2:15][C@@H:14]([CH3:16])[N:13]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[CH2:12][C@@H:11]2[CH3:25])=[O:9])=[C:4]([C:28]([OH:30])=O)[CH:3]=1.ClC(OCC(C)C)=O.[CH3:39][N:40]1CCOCC1.CN.O1CCCC1>>[Cl:1][C:2]1[CH:27]=[CH:26][C:5]([O:6][CH2:7][C:8]([N:10]2[CH2:15][C@@H:14]([CH3:16])[N:13]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[CH2:12][C@@H:11]2[CH3:25])=[O:9])=[C:4]([C:28]([NH:40][CH3:39])=[O:30])[CH:3]=1

Participants

6

Reactant 5

HCID 6329MethylamineHCID 79724-MethylmorpholineHCID 8028TetrahydrofuranHCID 62365Isobutyl chloroformateHCID 69104603HCID 69104603, compound

Product 1

HCID 69104936HCID 69104936, compoundYield 84.8%

Conditions

Temperature
0 °C

Procedure

To a solution of (trans)-1-((4-chloro-2-carboxyphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine (0.217 g, 0.50 mmol) in a solution of tetrahydroduran (5 mL) at 0° C. was added isobutyl chloroformate (0.075 g, 0.55 mmol) and N-methylmorpholine (0.0556 g, 0.55 mmol). The resulting mixture was stirred at 0° C. for 20 min, resulting in formation of a white precipitate. A solution of methylamine in tetrahydrofuran (0.25 mL, 2.0 M, 0.50 mmol) was then added and the mixture stirred for 30 min more, at which time it was concentrated of volatiles in vacuo. The resulting residue was dissolved in ethyl acetate and washed with water, then brine, dried over MgSO4, filtered and concentrated to 0.208 g of a foam. This was dissolved in ethyl acetate and treated with 1 M ethereal HCl solution (excess). The resulting solid was collected by filtration and washed with ethyl acetate. Drying in vacuo afforded 0.19 g of (trans)-1-((4-chloro-2-(methylaminocarbonyl)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine as a white solid; NMR (DMSO-d6) 10.8 (br d, 1), 9.2 (br s, 1), 7.8 (s, 2), 7.7 (m, 1), 7.6 (m, 1), 7.3 (m, 3), 5.4 (d, 1), 5.0 (m, 2), 4.7 (m, 1), 4.3 (m, 3), 4.0 (m, 1), 3.6 (m, 2), 2.8 (s, 3), 1.4 (m, 3), 1.3 (m, 3) ppm.

Workup

  1. customresulting in formation of a white precipitate
  2. stirringthe mixture stirred for 30 min more
  3. concentrationat which time it was concentrated of volatiles in vacuo
  4. dissolutionThe resulting residue was dissolved in ethyl acetate
  5. washwashed with water
  6. dry with materialbrine, dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated to 0.208 g of a foam
  9. dissolutionThis was dissolved in ethyl acetate
  10. additiontreated with 1 M ethereal HCl solution (excess)
  11. filtrationThe resulting solid was collected by filtration
  12. washwashed with ethyl acetate
  13. customDrying in vacuo

Sources & evidence

ORD record
ord-4d9fe3013a48402aada3a9af3efb44c0
Source dataset
uspto-grants-2007_09
Patent number
US07268140B2

Reaction notes

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