4-Methylmorpholine → HCID 53700144, compound

HRID 2288976Notes

Reaction equation

HRID 2288976 reaction equation
[C:1]([N:11]1[CH2:19][CH2:18][CH:14]([C:15]([OH:17])=O)[CH2:13][CH2:12]1)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].CN1CCOCC1.ClC(OCC(C)C)=O.Cl.[NH2:36][CH2:37][C:38]([C:40]1[CH:45]=[CH:44][C:43]([Cl:46])=[CH:42][CH:41]=1)=[O:39].S(=O)(=O)(O)[O-].[Na+]>ClCCl.C(OCC)(=O)C>[CH2:4]([O:3][C:1]([N:11]1[CH2:12][CH2:13][CH:14]([C:15](=[O:17])[NH:36][CH2:37][C:38]([C:40]2[CH:45]=[CH:44][C:43]([Cl:46])=[CH:42][CH:41]=2)=[O:39])[CH2:18][CH2:19]1)=[O:2])[C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1

Participants

8

Reactant 5

HCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 516919Sodium BisulfateHCID 7364891-Carbobenzoxy-4-piperidinecarboxylic AcidHCID 27982112-Amino-1-(4-chlorophenyl)ethan-1-one hydrochloride

Product 1

HCID 53700144HCID 53700144, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of N-carbobenzoxy-isonipecotic acid (10.49 g, 39.84 mmol) and 4-methylmorpholine (NMM) (500 mL, 45.0 mmol) in anhydrous dichloromethane (200 mL) under N2 and cooled in an -25° C. bath is added isobutyl chloroformate (5.30 mL, 40.0 mmol) dropwise. Following complete addition, the suspension is stirred for 5 min, then 2-amino-4'-chloroacetophenone hydrochloride (7.4632 g, 36.217 mmol), prepared as in Part A, is added, followed by NMM (10.10 mL, 90.94 mmol). After stirring in the -25° C. bath for 30 min, the suspension is allowed to warm to RT over 1.5 h. To the solid reaction mixture is added half-saturated aqueous sodium bisulfate, dichloromethane, and ethyl acetate. The solids are collected, washed with dichloromethane, and heated to reflux in THF (300 mL) for 30 min. The mixture is filtered and the filtrate concentrated to about 1/20th volume. Diethyl ether is added, the precipitated solids are collected, and dried in vacuo at RT to afford the product as fluffy, white solids.

Workup

  1. additionaddition
  2. additionis added
  3. stirringAfter stirring in the -25° C. bath for 30 min
  4. customTo the solid reaction mixture
  5. customThe solids are collected
  6. washwashed with dichloromethane
  7. temperatureheated
  8. temperatureto reflux in THF (300 mL) for 30 min
  9. filtrationThe mixture is filtered
  10. concentrationthe filtrate concentrated to about 1/20th volume
  11. additionDiethyl ether is added
  12. customthe precipitated solids are collected
  13. customdried in vacuo at RT
  14. customto afford the product as fluffy, white solids

Sources & evidence

ORD record
ord-b13261b5dbac4844af3ac57a7bbe4d5e
Source dataset
uspto-grants-2000_07
Patent number
US06090825

Reaction notes

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