4-Methylmorpholine → 3-(2-Chlorobenzyloxy)-5-[1-N-(tert-butoxycarbonyl)piperidin-4-yl]toluene

HRID 482101Notes

Reaction equation

HRID 482101 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14]O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:16][C:17]1[CH:32]=[CH:31][CH:30]=[CH:29][C:18]=1[CH2:19][O:20][C:21]1[CH:22]=C(O)[CH:24]=[C:25]([CH3:27])[CH:26]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CN1CCOCC1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[Cl:16][C:17]1[CH:32]=[CH:31][CH:30]=[CH:29][C:18]=1[CH2:19][O:20][C:21]1[CH:26]=[C:25]([CH3:27])[CH:24]=[C:14]([CH:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:12]2)[CH:22]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylateHCID 158950973-(2-Chlorobenzyloxy)-5-methylphenol

Product 1

HCID 190649793-(2-Chlorobenzyloxy)-5-[1-N-(tert-butoxycarbonyl)piperidin-4-yl]tolueneYield 70.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 177 mg (0.823 mmol) of N-tert-butoxycarbonyl-4-piperidinemethanol, as prepared in step f of Example 1, 195 mg (0.785 mmol) of 3-(2-chlorobenzyloxy)-5-methylphenol, as prepared in the preceding step, 262 mg (1.02 mmol) of triphenylphosphine, and 250 μL (2.27 mmol) of N-methylmorpholine in 3 mL of tetrahydrofuran was added 140 μL (0.892 mmol) of diethyl azodicarboxylate. The reaction mixture was stirred overnight, quenched with saturated NaCl (50 mL), and extracted into ethyl acetate (50 mL). The organic extract was dried (MgSO4), and the product was partially purified by flash chromatography (ethyl acetate/hexane (1:4)), to give 230 mg of impure title compound (contaminated with 3-(2-chlorobenzyloxy)-5-methylphenol). This material was used as is in the next reaction.

Workup

  1. customquenched with saturated NaCl (50 mL)
  2. extractionextracted into ethyl acetate (50 mL)
  3. extractionThe organic extract
  4. dry with materialwas dried (MgSO4)
  5. customthe product was partially purified by flash chromatography (ethyl acetate/hexane (1:4))

Sources & evidence

ORD record
ord-724f5fb9a4a34f08bcd6991c653332d5
Source dataset
uspto-grants-1998_08
Patent number
US05792769

Reaction notes

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