Aniline → HCID 86731821, compound

HRID 1846971Notes

Reaction equation

HRID 1846971 reaction equation
Cl.CN(C)CCCN=C=NCC.[C:13]([S:17]([CH2:20][C@@H:21]([N:25]1[C@H:30]([C:31]2[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=2)[C@@H:29]([C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([Cl:44])[CH:39]=2)[CH2:28][C@@:27]([CH2:46][C:47]([OH:49])=O)([CH3:45])[C:26]1=[O:50])[CH:22]1[CH2:24][CH2:23]1)(=[O:19])=[O:18])([CH3:16])([CH3:15])[CH3:14].[NH2:51][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1>>[C:13]([S:17]([CH2:20][C@@H:21]([N:25]1[C@H:30]([C:31]2[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=2)[C@@H:29]([C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([Cl:44])[CH:39]=2)[CH2:28][C@@:27]([CH2:46][C:47]([NH:51][C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)=[O:49])([CH3:45])[C:26]1=[O:50])[CH:22]1[CH2:23][CH2:24]1)(=[O:18])=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

4

Reactant 3

HCID 6115AnilineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68001087HCID 68001087, compound

Product 1

HCID 86731821HCID 86731821, compound

Procedure

N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC, 0.117 g, 0.612 mmol) was added to a solution of 2-((3R,5R,6S)-1-((S)-2-(tert-butylsulfonyl)-1-cyclopropylethyl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl)acetic acid (0.118 g, 0.204 mmol, Example 1, Step H) and aniline (0.020 mL, 0.225 mmol) at 0° C. After the addition was complete, the reaction mixture was removed from the ice bath and stirred at room temperature for 19 hours. The reaction mixture was diluted with ice-cold 1 M hydrochloric acid to adjust the pH to 1 and the solution was extracted twice with ether. The combined organic layer was washed with brine, dried over sodium sulfate, decanted and concentrated under a vacuum to provide an orange oil. Purification by flash chromatography (12 g SiO2 column, gradient elution of 15% to 100% ethyl acetate in hexanes provided the title compound as a white foam.

Workup

  1. additionAfter the addition
  2. customthe reaction mixture was removed from the ice bath
  3. additionThe reaction mixture was diluted with ice-cold 1 M hydrochloric acid
  4. extractionthe solution was extracted twice with ether
  5. washThe combined organic layer was washed with brine
  6. dry with materialdried over sodium sulfate
  7. customdecanted
  8. concentrationconcentrated under a vacuum
  9. customto provide an orange oil
  10. customPurification by flash chromatography (
  11. wash12 g SiO2 column, gradient elution of 15% to 100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-9b02d29a076342b0a03927110017f550
Source dataset
uspto-grants-2015_02
Patent number
US08952036B2

Reaction notes

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