4-Methylmorpholine → HCID 59708027, compound

HRID 252233Notes

Reaction equation

HRID 252233 reaction equation
[C:1]([CH:4]1[CH:9]2[O:10][CH:6]([CH2:7][CH2:8]2)[CH:5]1[CH2:11][C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1[O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)(O)=[O:2].[NH2:27][C@H:28]([C:31]([NH2:33])=[O:32])[CH2:29][OH:30].CN1[CH2:40][CH2:39]OCC1.CCN=C=N[CH2:46][CH2:47][CH2:48]N(C)C>CN(C)C=O>[CH:48]1([CH2:47][CH2:46][CH2:39][CH2:40][NH:33][C:31](=[O:32])[CH:28]([NH:27][C:1]([CH:4]2[CH:9]3[O:10][CH:6]([CH2:7][CH2:8]3)[CH:5]2[CH2:11][C:12]2[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=2[O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:2])[CH2:29][OH:30])[CH2:8][CH2:9][CH2:4][CH2:5][CH2:6]1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 101138L-SerinamideHCID 597080212-[[3-Carboxy-7-oxabicyclo[2.2.1]hept-2-yl]methyl]-4-fluoro-1-phenylmethoxybenzene

Product 1

HCID 59708027HCID 59708027, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of [1S-(1α, 2α, 3α, 4α)]-2-[[3-Carboxy-7-oxabicyclo[2.2.1]hept-2-yl]methyl]-4-fluoro-1-phenylmethoxybenzene (0.3 g, 0.825 mmol), N-(4-cyclohexyl)butyl)-L-serinamide (0.2 g, 0.825 mmol), HBOt (0.122 g, 0.91 mmol), 4-methylmorpholine (0.1 mL, 0.91 mmol) in dimethylformamide (5 mL), at 0° C. and under nitrogen atmosphere, was added portion-wise EDAC (0.174 g, 0.91 mmol). The resulting mixture was stirred for 10 minutes then it was allowed to warm slowly to room temperature and stirred for 16 h. After this time, the reaction was stopped and the solvent was evaporated under vacuum. The crude material was partitioned between ethyl acetate (15 mL) and 2M HCl (10 mL). The organic phase was separated; it was washed with a sat. solution of sodium bicarbonate (10 mL), Brine (10 mL), dried (MgSO4), filtered and the solvent evaporated “under vacuum” to give the titled product as an oil which was used in the next step without any additional purification. 1H-NMR (CDCl3, 300 MHz) δ 7.30 (m, 5H, ArH), 7.03 (t, 1H, J=5.8 Hz, CONH), 6.80 (m, 4H, ArH+NH), 5.03 (s, 2H, —OCH2Ph), 4.69 (d, 1H, J=5.1 Hz, —CH—O—), 4.42 (m, 1H, —CONHCHCO—), 4.33 (d, 1H, J=5.1 Hz, —CH—O—), 3.97 (dd, 1H, J=3.8, 11.3 Hz, —CH2OH), 3.56 (dd, 1H, J=5.5, 11.3 Hz, —CH2OH), 3.12 (m, 2H, —NCH2—), 2.73-2.40 (m, 4H, —CH—+—CH2—), 1.63-0.70 (m, 21H, —CH2—CH2—)

Workup

  1. stirringstirred for 16 h
  2. customthe solvent was evaporated under vacuum
  3. customThe crude material was partitioned between ethyl acetate (15 mL) and 2M HCl (10 mL)
  4. customThe organic phase was separated
  5. washit was washed with a sat. solution of sodium bicarbonate (10 mL), Brine (10 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customthe solvent evaporated “under vacuum”

Sources & evidence

ORD record
ord-b11905747baf4dc9834cb30ff6da31cd
Source dataset
uspto-grants-2011_01
Patent number
US07868032B2

Reaction notes

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