Tetrahydrofuran → HCID 21957316, compound

HRID 2213368Notes

Reaction equation

HRID 2213368 reaction equation
C1COCC1.[C:6]([NH:9][CH2:10][CH:11]([O:14][C:15](=[O:17])C)[CH2:12]Cl)(=[O:8])[CH3:7].C(OC(=O)[NH:27][C:28]1[CH:33]=[CH:32][C:31]([N:34]2[CH:39]=[CH:38][C:37](=[O:40])[CH2:36][CH2:35]2)=[CH:30][CH:29]=1)C1C=CC=CC=1>CN(C=O)C.CO>[O:17]=[C:15]1[N:27]([C:28]2[CH:33]=[CH:32][C:31]([N:34]3[CH:35]=[CH:36][C:37](=[O:40])[CH2:38][CH2:39]3)=[CH:30][CH:29]=2)[CH2:12][CH:11]([CH2:10][NH:9][C:6](=[O:8])[CH3:7])[O:14]1

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 53061521-Acetamido-3-chloropropan-2-yl acetateHCID 21051172HCID 21051172, compound

Product 1

HCID 21957316HCID 21957316, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

1.0 M LiOBu-t in THF (5 mL, 5 mmol) is added dropwise with stirring to a solution of acetic acid 1-(acetylamino-methyl)-2-chloro-ethyl ester (0.600 g, 3.10 mmol) in DMF (1 mL) and MeOH (0.127 mL) under nitrogen atmosphere at 0° C. [4-(4-Oxo-3,4-dihydro-2H-pyridin-1-yl)-phenyl]-carbamic acid benzyl ester (0.500 g, 1.55 mmol; prepared as described for Example 8), is added, and the mixture is allowed to gradually warm up to r.t. and stirred for additional 24 h. The mixture is quenched with saturated aq. NH4Cl (20 mL), diluted with aq. NaCl, and extracted with EtOAc (3×). The organic layers are combined and washed with brine, and dried over MgSO4. The solvent is removed under vacuum, and the crude product purified by silica gel flash chromatography (gradient 20% to 100% EtOAc—hexanes) to afford the title compound as a white solid. Yield 137 mg (26%). MS (m/z): 330 [M+H]+. 1H NMR (300 MHz, DMSO-d6) δ 8.24 (br. t, J=5.8 Hz, 1H), 7.72 (d, J=7.7, 1H), 7.53 (d, J=9.1, 2H), 7.27 (d, J=9.1, 2H), 4.97 (d, J=7.7 Hz, 1H), 4.72–4.67 (m, 1H), 4.10 (t, J=9.1 Hz, 2H), 3.75–3.69 (m, 1H), 3.40 (t, J=5.5 Hz, 2H), 2.50–2.49 (m, 2H), 1.82 (s, 3H).

Workup

  1. additionis added
  2. customThe mixture is quenched with saturated aq. NH4Cl (20 mL)
  3. additiondiluted with aq. NaCl
  4. extractionextracted with EtOAc (3×)
  5. washwashed with brine
  6. dry with materialdried over MgSO4
  7. customThe solvent is removed under vacuum
  8. customthe crude product purified by silica gel flash chromatography (gradient 20% to 100% EtOAc—hexanes)

Sources & evidence

ORD record
ord-5e944ef4bb2d4c5b881abb86bb86fd49
Source dataset
uspto-grants-2006_09
Patent number
US07105547B2

Reaction notes

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