Acetic Acid → Methyl 3-[2-(2,6-bis-hydroxymethyl-pyridin-4-yloxy)-ethylamino]-propanoate

HRID 2173758Notes

Reaction equation

HRID 2173758 reaction equation
[OH:1][CH2:2][C:3]1[CH:8]=[C:7]([O:9][CH2:10][CH2:11][NH:12][CH2:13][CH2:14][C:15]([O:17][C:18](C)(C)C)=[O:16])[CH:6]=[C:5]([CH2:22][OH:23])[N:4]=1.C(O)(C(F)(F)F)=O.C[Si](C=[N+]=[N-])(C)C.C(O)(=O)C>C(Cl)Cl.CO.CCCCCC.O.CCOC(C)=O>[OH:23][CH2:22][C:5]1[CH:6]=[C:7]([O:9][CH2:10][CH2:11][NH:12][CH2:13][CH2:14][C:15]([O:17][CH3:18])=[O:16])[CH:8]=[C:3]([CH2:2][OH:1])[N:4]=1

Participants

10

Reactant 4

HCID 176Acetic AcidHCID 6422Trifluoroacetic acidHCID 167693TrimethylsilyldiazomethaneHCID 66716290Tert-butyl 3-[2-(2,6-bis-hydroxymethyl-pyridin-4-yloxy)-ethylamino]-propanoate

Product 1

HCID 66714165Methyl 3-[2-(2,6-bis-hydroxymethyl-pyridin-4-yloxy)-ethylamino]-propanoateYield 26.6%

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 670 mg of tert-butyl 3-[2-(2,6-bis-hydroxymethyl-pyridin-4-yloxy)-ethylamino]-propanoate in 20 ml of DCM was added 2 ml of TFA. The mixture was stirred for 6 hours at room temperature and then concentrated under reduced pressure, taken up in DCM and concentrated again under reduced pressure. To the residue obtained, dissolved in 10 ml of MeOH, was added, at 5° C., 7 ml of a 2M solution of (trimethylsilyl)diazomethane in hexane. The mixture was stirred for 1 hour 30 minutes at 5° C. and then 200 μl of acetic acid were added. The mixture was taken up in 30 ml of water and 30 ml of EtOAc. The aqueous phase was extracted 2× with 30 ml of EtOAc. The organic phases were combined, washed with saturated NaCl solution, concentrated under reduced pressure and purified by flash chromatography on silica (Analogix Super Flash SiO2 SF15-24g), using a gradient of 0 to 10% MeOH in DCM. The fractions containing the desired product were combined and concentrated under reduced pressure. 155 mg of methyl 3-[2-(2,6-bis-hydroxymethyl-pyridin-4-yloxy)-ethylamino]-propanoate were obtained. LC/MS (C): tr=2.56 min; [M+H]+: m/z 470.

Workup

  1. concentrationconcentrated under reduced pressure
  2. concentrationconcentrated again under reduced pressure
  3. customTo the residue obtained
  4. additionwas added, at 5° C.
  5. stirringThe mixture was stirred for 1 hour 30 minutes at 5° C.
  6. extractionThe aqueous phase was extracted 2× with 30 ml of EtOAc
  7. washwashed with saturated NaCl solution
  8. concentrationconcentrated under reduced pressure
  9. custompurified by flash chromatography on silica (Analogix Super Flash SiO2 SF15-24g)
  10. additionThe fractions containing the desired product
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-840cb5b71dc34c368aa3a1024273d0b0
Source dataset
uspto-grants-2015_06
Patent number
US09056914B2

Reaction notes

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