2-(Methylamino)ethanol → HCID 58024758, compound

HRID 1675676Notes

Reaction equation

HRID 1675676 reaction equation
[CH3:1][NH:2][CH2:3][CH2:4][OH:5].C(N(CC)C(C)C)(C)C.Br[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]([NH:25][C:26]1[CH:38]=[CH:37][C:29]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[CH:28][CH:27]=1)=[O:24]>CN(C)C=O>[OH:5][CH2:4][CH2:3][N:2]([CH3:1])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]([NH:25][C:26]1[CH:38]=[CH:37][C:29]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[CH:28][CH:27]=1)=[O:24]

Participants

5

Reactant 3

HCID 80162-(Methylamino)ethanolHCID 81531DiisopropylethylamineHCID 58024775HCID 58024775, compound

Product 1

HCID 58024758HCID 58024758, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

To a solution of 2-(methylamino)ethanol (10.7 g, 11.5 ml, 144 mmol, 1.5 equivalents, commercially available e.g. from Aldrich) in dry N,N-dimethylformamide (300 ml) was added N,N-diisopropylethylamine (25 ml, 18.5 g, 144 mmol, 1.5 equivalents). To this mixture was added 1,1-dimethylethyl 4-[(8-bromooctanoyl)amino]benzoate (38.1 g, 96 mmol, 1 equivalent) in dry N,N-dimethylformamide (250 ml) over 12 minutes. The mixture was then heated to and at about 60° C. for 4.25 hours. The mixture was then cooled and the solvent was removed by evaporation using high vacuum to give a golden oil. An attempt to partition this oil between water and ethyl acetate gave a cloudy organic phase and phase separation was poor; an oil separated out as a third layer, some of which was collected and evaporated to give crude product (16.69 g). The remaining emulsion was allowed to stand overnight, giving a clear organic layer which was decanted off, dried (MgSO4) and evaporated to give further crude product as a golden oil (28.11 g). Attempts to further extract the aqueous phase with ethyl acetate or dichloromethane gave an emulsion again, from which further crude product (about 10 g) was finally isolated. The combined crude product was purified by chromatography on silica gel (about 1400 ml of 7734 silica), eluting with 5% methanol in dichloromethane, then 8% methanol in dichloromethane, then 10% methanol in dichloromethane, and finally 20% and 30% methanol in dichloromethane, to afford the title compound as a white foam (28.4 g). LCMS showed MH+=393; TRET=2.52 min.

Workup

  1. temperatureThe mixture was then cooled
  2. customthe solvent was removed by evaporation
  3. customto give a golden oil
  4. customAn attempt to partition this oil between water and ethyl acetate
  5. customgave
  6. customa cloudy organic phase and phase separation
  7. customan oil separated out as a third layer
  8. customsome of which was collected
  9. customevaporated
  10. customto give crude product (16.69 g)
  11. customgiving a clear organic layer which
  12. customwas decanted off
  13. dry with materialdried (MgSO4)
  14. customevaporated
  15. customto give further crude product as a golden oil (28.11 g)
  16. extractionto further extract the aqueous phase with ethyl acetate or dichloromethane
  17. customgave an emulsion again

Sources & evidence

ORD record
ord-69e5fc81fe1d4c5f80cf3afbe65a770b
Source dataset
uspto-grants-2011_08
Patent number
US08003663B2

Reaction notes

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