Dimethylamine → HCID 11745503, compound

HRID 1671455Notes

Reaction equation

HRID 1671455 reaction equation
[C:1]1([CH2:7][O:8][CH2:9][C:10]([OH:12])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:13]1([N:19]=[C:20]=NC2CCCCC2)CCCCC1.O=C1C2C=CC=CC=2C(=O)N1CCCS(OCC(C)(C)[C@@H](OCC1C=CC=CC=1)C(O)=O)(=O)=O.CNC>ClCCl.O1CCCC1>[CH3:13][N:19]([CH3:20])[C:10](=[O:12])[CH2:9][O:8][CH2:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 4

HCID 674DimethylamineHCID 10868DicyclohexylcarbodiimideHCID 290301(Benzyloxy)acetic acidHCID 86628888HCID 86628888, compound

Product 1

HCID 11745503HCID 11745503, compoundYield 65.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Adapting procedures or variations thereof according to Benington et al., J. Org. Chem. 1961, 26, 194-197; and Griffiths et al., Tetrahedron, 1997, 53(52), 17815-17822, a 250 mL round-bottomed flask equipped with a magnetic stirring bar and rubber septum was charged with 1.22 mL (1.41 g, 8.51 mmol) of 2-(phenylmethoxy)acetic acid. The acid was dissolved in 30 mL of anhydrous dichloromethane (DCM). To the solution was added 1.86 g (9.0 mmol) of dicyclohexylcarbodiimide (DCC) and the reaction mixture was stirred for two hours at room temperature. Twenty (20) mL (40 mmol) of a two molar (2 M) solution of dimethyl amine (Me2NH) in tetrahydrofuran was added and the mixture stirred overnight at room temperature. The precipitated dicyclohexyl urea (DCU) was filtered off and the solvents removed under reduced pressure using a rotary evaporator. The residue was diluted with ethyl acetate (EtOAc) and the solution filtered again to remove residual DCU. The solution was washed successively with one molar (1.0 M) hydrochloric acid, a saturated aqueous solution of sodium hydrogen carbonate (NaHCO3), brine, dried over anhydrous magnesium sulfate (MgSO4), filtered, and the solvent removed under reduced pressure using a rotary evaporator to yield a brown solid. Final purification by silica gel column chromatography using a mixture of ethyl acetate (EtOAc) and hexane (Hxn) as eluent (EtOAc/Hxn=1:9) provided 1.08 g (65% yield) of the title compound (36a). Rf=0.30 (EtOAc/Hxn=1:9). 1H NMR (400 MHz, CDCl3): δ=2.97 (s, 3H), 2.99 (s, 3H), 4.18 (s, 2H), 4.62 (s, 2H), 7.28-7.37 (m, 5H) ppm. MS (ESI) m/z: 194.1 (M+H)+, 216.1 (M+Na)+. The analytical data was consistent with the proposed structure and the data in the literature.

Workup

  1. customand Griffiths et al., Tetrahedron, 1997, 53(52), 17815-17822, a 250 mL round-bottomed flask equipped with a magnetic stirring bar
  2. stirringthe mixture stirred overnight at room temperature
  3. filtrationThe precipitated dicyclohexyl urea (DCU) was filtered off
  4. customthe solvents removed under reduced pressure
  5. customa rotary evaporator
  6. additionThe residue was diluted with ethyl acetate (EtOAc)
  7. filtrationthe solution filtered again
  8. customto remove residual DCU
  9. washThe solution was washed successively with one molar (1.0 M) hydrochloric acid
  10. dry with materiala saturated aqueous solution of sodium hydrogen carbonate (NaHCO3), brine, dried over anhydrous magnesium sulfate (MgSO4)
  11. filtrationfiltered
  12. customthe solvent removed under reduced pressure
  13. customa rotary evaporator
  14. customto yield a brown solid
  15. customFinal purification by silica gel column chromatography
  16. additiona mixture of ethyl acetate (EtOAc) and hexane (Hxn) as eluent (EtOAc/Hxn=1:9)

Sources & evidence

ORD record
ord-4f1123b2edfb46d984f26a0434536d0f
Source dataset
uspto-grants-2011_08
Patent number
US07994218B2

Reaction notes

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