Acetic Acid → HCID 89586066, compound

HRID 2173762Notes

Reaction equation

HRID 2173762 reaction equation
[OH:1][CH2:2][C:3]1[CH:8]=[C:7]([O:9][CH2:10][CH2:11][N:12]([C:23](=[O:37])[CH2:24][CH2:25][O:26][CH2:27][CH2:28][O:29][CH2:30][CH2:31][O:32][CH2:33][CH2:34][O:35][CH3:36])[CH2:13][CH2:14][CH2:15][C:16]([O:18][C:19](C)(C)C)=[O:17])[CH:6]=[C:5]([CH2:38][OH:39])[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>[OH:39][CH2:38][C:5]1[CH:6]=[C:7]([O:9][CH2:10][CH2:11][N:12]([C:23](=[O:37])[CH2:24][CH2:25][O:26][CH2:27][CH2:28][O:29][CH2:30][CH2:31][O:32][CH2:33][CH2:34][O:35][CH3:36])[CH2:13][CH2:14][CH2:15][C:16]([O:18][CH3:19])=[O:17])[CH:8]=[C:3]([CH2:2][OH:1])[N:4]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 6422Trifluoroacetic acidHCID 167693TrimethylsilyldiazomethaneHCID 66716217HCID 66716217, compound

Product 1

HCID 89586066HCID 89586066, compoundYield 62.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8058HexaneSolvent

Procedure

To a solution of 460 mg of tert-butyl 4-[[2-(2,6-bis-hydroxymethyl-pyridin-4-yloxy)-ethyl]-(3-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy}-propionyl)-amino]-butanoate in 7 ml of DCM were added 1.14 ml of TFA. The mixture was stirred for 15 hours at room temperature and then concentrated under reduced pressure. To the residue obtained, dissolved in 3.8 ml of MeOH, was added, at 50° C., 3.1 ml of a 2M solution of (trimethylsilyl)diazomethane in hexane. The mixture was stirred for 1 hour at 5° C. and 100 μl of acetic acid were then added. After concentration under reduced pressure, the residue obtained was purified by flash chromatography on silica (Analogix Super Flash SiO2 SF25-40g), using a gradient of 2 to 10% MeOH in DCM. The fractions containing the desired product were combined and concentrated under reduced pressure. 265 mg of methyl 4-[[2-(2,6-bis-hydroxymethyl-pyridin-4-yloxy)-ethyl]-(3-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy}-propionyl)-amino]-butanoate were obtained. 1H NMR (400 MHz, DMSO-d6): 50%-50% mixture of conformers with: 1.67 to 1.86 (m, 2H); 2.27 (t, J=7.3 Hz, 1H); 2.36 (t, J=7.3 Hz, 1H); 2.57 (t, J=6.7 Hz, 1H); 2.66 (t, J=6.7 Hz, 1H); 3.23 (s, 3H); 3.31 to 3.75 (m, 21H); 4.14 (t, J=5.6 Hz, 1H); 4.19 (t, J=5.6 Hz, 1H); 4.45 (m, 4H); 5.30 (m, 2H); 6.84 (s, 1H); 6.86 (s, 1H). LC/MS (G): tr=0.62 min; [M+H]+: m/z 517; [M−H+HCO2H]−: m/z 561

Workup

  1. concentrationconcentrated under reduced pressure
  2. customTo the residue obtained
  3. additionwas added, at 50° C.
  4. stirringThe mixture was stirred for 1 hour at 5° C.
  5. concentrationAfter concentration under reduced pressure
  6. customthe residue obtained
  7. customwas purified by flash chromatography on silica (Analogix Super Flash SiO2 SF25-40g)
  8. additionThe fractions containing the desired product
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e4fab7ee8a83485392e981c9a9b1c39f
Source dataset
uspto-grants-2015_06
Patent number
US09056914B2

Reaction notes

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