3,5-Dimethylaniline → HCID 9255731, compound

HRID 1466464Notes

Reaction equation

HRID 1466464 reaction equation
[C:1]([N:8]1[CH2:15][CH2:14][CH2:13][C@H:9]1[C:10]([OH:12])=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CCN(CC)CC.ClC(OCC)=O.[CH3:29][C:30]1[CH:31]=[C:32]([CH:34]=[C:35]([CH3:37])[CH:36]=1)[NH2:33]>C(Cl)Cl.[Cl-].[Na+].O>[CH3:29][C:30]1[CH:31]=[C:32]([NH:33][C:10]([C@@H:9]2[CH2:13][CH2:14][CH2:15][N:8]2[C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])=[O:12])[CH:34]=[C:35]([CH3:37])[CH:36]=1

Participants

7

Reactant 4

HCID 79493,5-DimethylanilineHCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-

Product 1

HCID 9255731HCID 9255731, compoundYield 119.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

Commercially available Boc-L-proline (16, 2.3 g; 10.7 mmol) is dissolved in DCM (20 ml) and cooled to 0° C. followed by the addition of NEt3 (1.12 g; 11.22 mmol) and ethyl chloroformate (1.22 g; 11.22 mmol) and finally commercially available 3,5-dimethylaniline (15) (1.36 g; 11.22 mmol). The reaction mixture is stirred at rt for 60 minutes. Brine (50 ml) is added and the organic layer is separated. The aq. layer is extracted with DCM (2×30 ml). The combined organic layers are dried over MgSO4, filtered and the solvent is removed under reduced pressure to give 4.07 g of crude (S)-tert-butyl 2-((3,5-dimethylphenyl)carbamoyl)pyrrolidine-1-carboxylate (17) which is used in the next step without further purification. LC-MS: tR=0.81 min; [M+H]+=319.11.

Workup

  1. customthe organic layer is separated
  2. extractionThe aq. layer is extracted with DCM (2×30 ml)
  3. dry with materialThe combined organic layers are dried over MgSO4
  4. filtrationfiltered
  5. customthe solvent is removed under reduced pressure

Sources & evidence

ORD record
ord-b1806397efa343f88399203cc1653153
Source dataset
uspto-grants-2015_04
Patent number
US09000029B2

Reaction notes

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