4-Methylmorpholine → HCID 86613244, compound

HRID 1660709Notes

Reaction equation

HRID 1660709 reaction equation
[CH2:1]([O:8][C:9](=[O:15])[C@@H:10]1[CH2:14][CH2:13][CH2:12][NH:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN1[CH2:22][CH2:21][O:20][CH2:19]C1.C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>CN(C=O)C.C(Cl)Cl>[CH2:1]([O:8][C:9](=[O:15])[C@@H:10]1[CH2:14][CH2:13][CH2:12][N:11]1[CH2:22][CH:21]1[O:20][CH2:19]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 736155Benzyl L-prolinate

Product 1

HCID 86613244HCID 86613244, compoundYield 74.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of L-proline benzyl ester (156 mg, 0.49 mmol) in DMF (2 mL), cooled to 0° C., NMM (56 μL, 0.53 mmol) and HOBt (198 mg, 1.47 mmol) were added. The solution was stirred at 0° C. for 15 minutes and a solution of glycidic acid21 (100 mg, 1.13 mmol) in CH2Cl2 (2 mL) was added. Finally a solution of DCC (253 mg, 1.23 mmol) in CH2Cl2 (2 mL) was added. The mixture was stirred 16 h at room temperature and filtered to remove the precipitate. The residue was diluted with CH2Cl2 (10 mL) and washed with 10% KHSO4 (10 mL), 5% NaHCO3 (10 mL) and NaCl (10 mL, sat), dried (Na2SO4), filtered and concentrated. The crude oil was purified by column chromatography (silica gel, EtOAc/Hexanes 1/1) to yield 120 (95 mg, 70%) as white foam. Rf 0.26 (AcOEt/Hexanes 1/1). 1H-NMR (500 MHz, CDCl3): mixture of rotamers 1.87-1.92 (m, 2H), 1.91-1.98 (m, 2H), 1.99-2.03 (m, 1H), 2.19-2.20 (m, 2H), 2.20-2.22 (m, 1H), 2.66-2.68 (m, 1H), 2.80-2.82 (m, 1H), 2.94-2.95 (m, 2H), 3.30-3.31 (m, 1H), 3.56-3.57 (m, 2H), 357-370 (m, 2H), 3.72-3.85 (m, 1H), 4.57-4.59 (m, 1H), 4.70-4.72 (m, 1H), 5.16 (s, 2H), 5.22-5.29 (m, 2H), 7.25-7.38 (m, 10H). 13C-NMR (125 MHz, CDCl3): 22.2, 24.9, 28.7, 30.9, 31.5, 45.9, 46.3, 46.4, 47.2, 48.0, 48.5, 58.7, 59.3, 66.9, 67.4, 128.1, 128.2, 128.4, 128.5, 128.7, 170.0, 182.3. HRMS m/z cald for C15H17NO4a (M+Na): 298.1055 found 298.1047.

Workup

  1. stirringThe mixture was stirred 16 h at room temperature
  2. filtrationfiltered
  3. customto remove the precipitate
  4. additionThe residue was diluted with CH2Cl2 (10 mL)
  5. washwashed with 10% KHSO4 (10 mL), 5% NaHCO3 (10 mL) and NaCl (10 mL, sat)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude oil was purified by column chromatography (silica gel, EtOAc/Hexanes 1/1)

Sources & evidence

ORD record
ord-7a19f0778ae04a5f89e02659a967144b
Source dataset
uspto-grants-2011_10
Patent number
US08030279B2

Reaction notes

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