4-Methylmorpholine → HCID 66688142, compound

HRID 1971860Notes

Reaction equation

HRID 1971860 reaction equation
[NH:1]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@@H:2]([C:10]([OH:12])=O)[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.CN1CCOCC1.ClC(OCC(C)C)=O.[O:35]1[CH2:40][CH2:39][CH:38]([CH2:41][N:42]2[CH2:47][CH2:46][CH:45]([CH2:48][NH2:49])[CH2:44][CH2:43]2)[CH2:37][CH2:36]1.[OH-].[Na+]>ClCCl>[C:16]([O:15][C:13](=[O:14])[NH:1][C@@H:2]([C:10](=[O:12])[NH:49][CH2:48][CH:45]1[CH2:44][CH2:43][N:42]([CH2:41][CH:38]2[CH2:37][CH2:36][O:35][CH2:40][CH2:39]2)[CH2:47][CH2:46]1)[CH2:3][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1)([CH3:19])([CH3:18])[CH3:17]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 14798Sodium HydroxideHCID 62365Isobutyl chloroformateHCID 637610Boc-D-phenylalanineHCID 22313260HCID 22313260, compound

Product 1

HCID 66688142HCID 66688142, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution consisting of 10 g of Boc-D-Phe-OH, 40 ml of dichloromethane and 4.6 ml of N-methylmorpholine is slowly dripped into a solution of 5.4 ml of isobutyl chloroformate in 60 ml of dichloromethane cooled to 0° C., at a rate such that the inner temperature does not exceed 5° C. The resulting mixture is maintained under stirring at 0° C. for 1 hour. A solution consisting of 8.0 g of (11) in 20 ml of dichloromethane is dripped into the reaction mixture at a rate such that the temperature does not exceed 5° C. The solution is maintained under stirring at 0° C. for 1 hour, and at ambient temperature for 5 hours. After a process control, 100 ml of 1M NaOH is added to the mixture, the two phases are separated, the organic phase is washed with water (2×), and after a low-pressure solvent change with ethyl acetate compound (12) is crystallised from ethyl acetate, to obtain 14.29 g of white solid. Yield 83%.

Workup

  1. customdoes not exceed 5° C
  2. temperatureThe resulting mixture is maintained
  3. customdoes not exceed 5° C
  4. temperatureThe solution is maintained
  5. stirringunder stirring at 0° C. for 1 hour
  6. waitat ambient temperature for 5 hours
  7. customthe two phases are separated
  8. washthe organic phase is washed with water (2×)
  9. customafter a low-pressure solvent change with ethyl acetate compound (12) is crystallised from ethyl acetate

Sources & evidence

ORD record
ord-f637dfebf9734df4a637f0668b41e58e
Source dataset
uspto-grants-2013_04
Patent number
US08431684B2

Reaction notes

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