Methanol → HCID 71278867, compound

HRID 1749886Notes

Reaction equation

HRID 1749886 reaction equation
[OH:1][C:2]1[CH:11]=[CH:10][C:5]2[C:6](=[O:9])[CH2:7][O:8][C:4]=2[C:3]=1[CH:12]([N:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1)[CH3:13].CO.[C:29]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.C1(C)C=CC=CC=1>O1CCCC1.C(OCC)(=O)C.CCCCCC>[CH3:29][O:1][C:2]1[CH:11]=[CH:10][C:5]2[C:6](=[O:9])[CH2:7][O:8][C:4]=2[C:3]=1[CH:12]([N:14]1[CH2:15][CH2:16][N:17]([C:20]([O:22][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:21])[CH2:18][CH2:19]1)[CH3:13]

Participants

9

Reactant 5

HCID 887MethanolHCID 1140TolueneHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 71278653HCID 71278653, compound

Product 1

HCID 71278867HCID 71278867, compoundYield 12%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of tert-butyl 4-[1-(6-hydroxy-3-oxo-2,3-dihydrobenzofuran-7-yl)ethyl]piperazine-1-carboxylate (0.75 g, 2.1 mmol) synthesized in Example B7, Step 2 in tetrahydrofuran (20 mL) was added with methanol (0.20 g, 6.3 mmol), and triphenylphosphine (0.65 g, 2.5 mmol). The reaction mixture was stirred at 0° C. under an argon atmosphere, and added dropwise with a 40% solution of diethyl azodicarboxylate in toluene (1.91 g, 4.4 mmol). After completion of the addition, the mixture was stirred at 40° C. for 20 hours. The solvent was evaporated under reduced pressure, and the residue was subjected to silica gel column chromatography (eluted with hexane/ethyl acetate (85:15→0:100)) to obtain a solid containing the objective substance. The solid was suspended in a mixed solvent of hexane and ethyl acetate and thereby washed, and the insoluble matter was removed by filtration. The filtrate was concentrated, the residue was subjected to silica gel column chromatography (aminopropyl silica was used, eluted with hexane/ethyl acetate (2:1→1:3)) to obtain tert-butyl 4-[1-(6-methoxy-3-oxo-2,3-dihydrobenzofuran-7-yl)ethyl]piperazine-1-carboxylate (0.091 g, 12%).

Workup

  1. additionAfter completion of the addition
  2. stirringthe mixture was stirred at 40° C. for 20 hours
  3. customThe solvent was evaporated under reduced pressure
  4. washthe residue was subjected to silica gel column chromatography (eluted with hexane/ethyl acetate (85:15→0:100))
  5. customto obtain a solid
  6. additioncontaining the objective substance
  7. washwashed
  8. customthe insoluble matter was removed by filtration
  9. concentrationThe filtrate was concentrated
  10. washthe residue was subjected to silica gel column chromatography (aminopropyl silica was used, eluted with hexane/ethyl acetate (2:1→1:3))

Sources & evidence

ORD record
ord-ddd4f9b824064f689da0ef7f79fccc4a
Source dataset
uspto-grants-2015_10
Patent number
US09156827B2

Reaction notes

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