4-Methylmorpholine → HCID 66650393, compound

HRID 419700Notes

Reaction equation

HRID 419700 reaction equation
C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH2:12][CH:13]([CH3:27])[C:14]([C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([C:23]([F:26])([F:25])[F:24])[CH:17]=1)=[O:15].[C:28]([N:35]1[CH2:40][CH2:39][CH:38]([C:41](O)=[O:42])[CH2:37][CH2:36]1)([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29].CN1CCOCC1.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>CCOC(C)=O.CN(C)C=O>[C:31]([O:30][C:28]([N:35]1[CH2:40][CH2:39][CH:38]([C:41](=[O:42])[NH:12][CH:13]([CH3:27])[C:14]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[C:18]([C:23]([F:26])([F:24])[F:25])[CH:17]=2)=[O:15])[CH2:37][CH2:36]1)=[O:29])([CH3:34])([CH3:33])[CH3:32]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 111923Propylphosphonic anhydrideHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 86632014HCID 86632014, compound

Product 1

HCID 66650393HCID 66650393, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Add dimethylformamide (20 mL) is to a mixture of 2-amino-1-(4-fluoro-3-trifluoromethyl-phenyl)-propan-1-one toluene-4-sulfonic acid salt (900 mg; 1.00 equiv; 2.21 mmoles) and 1-Boc-piperidine-4-carboxylic acid (Boc-Inp-OH) (613.96 mg, 1.20 equiv; 2.65 mmoles) at room temperature. Add N-methylmorpholine (6.00 equiv; 13.26 mmoles; 1.46 mL) to the above solution, then 1-propanephosphonic acid cyclic anhydride (1.50 equiv; 3.31 mmoles; 862.14 μL) at 0° C. Warm the mixture to room temperature while stirring for one hour. Dilute the mixture with EtOAc, wash with water, 1M citric acid, water, saturated NaHCO3, and saturated aqueous sodium chloride and dry over Na2SO4. Purify the residue by dissolving in CH2Cl2, loading onto a silica gel column and eluting with EtOAc to give 500 mg (51%) of the title compound.

Workup

  1. customat 0° C
  2. washwash with water, 1M citric acid, water, saturated NaHCO3, and saturated aqueous sodium chloride
  3. dry with materialdry over Na2SO4
  4. customPurify the residue
  5. dissolutionby dissolving in CH2Cl2
  6. washeluting with EtOAc

Sources & evidence

ORD record
ord-3226e145397f4a55a88e8588f51f6939
Source dataset
uspto-grants-2012_01
Patent number
US08093383B2

Reaction notes

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