4-Methylmorpholine → tert-Butyl 4-[(2E)-4-methoxy-4-oxobut-2-en-1-yl]piperidine-1-carboxylate

HRID 361784Notes

Reaction equation

HRID 361784 reaction equation
C(Cl)(=O)C(Cl)=O.[C:7]([N:14]1[CH2:19][CH2:18][CH:17]([CH2:20][CH2:21]O)[CH2:16][CH2:15]1)([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8].CN1CCOCC1.[CH3:30][O:31][C:32]([CH:34]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)=[O:33]>C(Cl)Cl.CS(C)=O>[CH3:30][O:31][C:32](=[O:33])/[CH:34]=[CH:21]/[CH2:20][CH:17]1[CH2:16][CH2:15][N:14]([C:7]([O:9][C:10]([CH3:11])([CH3:12])[CH3:13])=[O:8])[CH2:19][CH2:18]1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 17453Acetic acid, 2-(triphenylphosphoranylidene)-, methyl esterHCID 65578Oxalyl chlorideHCID 8541401-(tert-Butoxycarbonyl)-4-(2-hydroxyethyl)piperidine

Product 1

HCID 10446560tert-Butyl 4-[(2E)-4-methoxy-4-oxobut-2-en-1-yl]piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of oxalyl chloride (11.8 g) in methylene chloride (180 ml) iscooled to -78° C. and dimethyl sulfoxide (DMSO) (8.9 ml) is added dropwise. The solution is stirred at -78° C. for about 3 minutes and a solution of N-BOC-2-(piperidin-4-yl)ethanol (14.3 g) in methylene chloride (250 ml) is added over a period of about 10 minutes. The solutionis stirred for about 1 hour and N-methyl morpholine (21.6 g) is added over a period of about 15 minutes. The solution is allowed to warm to room temperature and, after about 30 minutes, methyl (triphenylphosphoranylidene) acetate (68.6 g) is added. The solution is stirred at room temperature for about 18 hours, evaporated in vacuo and the residue taken up in ethyl acetate. The ethyl acetate solution is washed with water, 5% HCl, 5% sodium hypochlorite solution, water, brine, dried over sodium sulfate, filtered and evaporated in vacuo to give methyl4-(N-BOC-piperidin-4-yl)trans-crotonate.

Workup

  1. customiscooled to -78° C.
  2. stirringThe solutionis stirred for about 1 hour
  3. temperatureto warm to room temperature and, after about 30 minutes
  4. stirringThe solution is stirred at room temperature for about 18 hours
  5. customevaporated in vacuo
  6. washThe ethyl acetate solution is washed with water, 5% HCl, 5% sodium hypochlorite solution, water, brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. customevaporated in vacuo

Sources & evidence

ORD record
ord-8f4792565f4242babd00081fbdfaff69
Source dataset
uspto-grants-1999_02
Patent number
US05866685

Reaction notes

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