1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → tert-butyl(S)-1-(2-(3,5-dichlorophenylamino)acetyl)piperidin-3-ylcarbamate

HRID 919594Notes

Reaction equation

HRID 919594 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][C@H:3]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:2]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[Cl:36][C:37]1[CH:38]=[C:39]([NH:44][CH2:45][C:46](O)=[O:47])[CH:40]=[C:41]([Cl:43])[CH:42]=1.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[Cl:36][C:37]1[CH:38]=[C:39]([NH:44][CH2:45][C:46]([N:1]2[CH2:6][CH2:5][CH2:4][C@H:3]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:11])([CH3:13])[CH3:12])[CH2:2]2)=[O:47])[CH:40]=[C:41]([Cl:43])[CH:42]=1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 1514171tert-butyl N-[(3S)-piperidin-3-yl]carbamateHCID 13138167(3,5-Dichlorophenyl)glycine

Product 1

HCID 69676426tert-butyl(S)-1-(2-(3,5-dichlorophenylamino)acetyl)piperidin-3-ylcarbamateYield 98%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of tert-butyl(S)-piperidin-3-ylcarbamate (500 mg, 2.5 mmol), in DMF (5 mL) was added EDCI (573 mg, 3.0 mmol), HOBt (405 mg, 3.0 mmol), 2-(3,5-dichlorophenylamino)acetic acid (550 mg, 2.5 mmol) and DIEA (0.5 mL, 3.0 mmol) at 0° C. The reaction mixture was stirred at rt overnight, the reaction mixture was diluted with EtOAc and washed with water. The water layer was extracted with the EtOAc and the combined organic layer was dried over Na2SO4 and evaporated in vacuo to give the crude compound that was purified by column chromatography (silica gel, gradient MeOH in CH2Cl2) to afford (900 mg, 98%) of the titled intermediate. LCMS: m/z: [M+1]=402.

Workup

  1. washwashed with water
  2. extractionThe water layer was extracted with the EtOAc
  3. dry with materialthe combined organic layer was dried over Na2SO4
  4. customevaporated in vacuo
  5. customto give the crude compound that
  6. customwas purified by column chromatography (silica gel, gradient MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-86850e8ba64545f0ad05abdb7aac3483
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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