1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Rac-((1r,2s)-2-{4-[cyclopropyl-(3-trifluoromethyl-benzenesulfonyl)-amino]-piperidine-1-carbonyl}-cyclopentyl)-carbamic acid tert-butyl ester

HRID 1428957Notes

Reaction equation

HRID 1428957 reaction equation
[CH:1]1([N:4]([CH:18]2[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]2)[S:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)(=[O:7])=[O:6])[CH2:3][CH2:2]1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[C:45]([O:49][C:50]([NH:52][C@H:53]1[CH2:57][CH2:56][CH2:55][C@H:54]1[C:58](O)=[O:59])=[O:51])([CH3:48])([CH3:47])[CH3:46]>C(Cl)Cl.C(Cl)(Cl)Cl>[C:45]([O:49][C:50](=[O:51])[NH:52][C@@H:53]1[CH2:57][CH2:56][CH2:55][C@@H:54]1[C:58]([N:21]1[CH2:22][CH2:23][CH:18]([N:4]([CH:1]2[CH2:3][CH2:2]2)[S:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:15])[F:16])[CH:9]=2)(=[O:6])=[O:7])[CH2:19][CH2:20]1)=[O:59])([CH3:48])([CH3:46])[CH3:47]

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 1268160(1R,2S)-2-(tert-Butoxycarbonylamino)cyclopentanecarboxylic acidHCID 2773944N-Cyclopropyl-N-piperidin-4-yl-3-(trifluoromethyl)benzenesulfonamide

Product 1

HCID 69026004Rac-((1r,2s)-2-{4-[cyclopropyl-(3-trifluoromethyl-benzenesulfonyl)-amino]-piperidine-1-carbonyl}-cyclopentyl)-carbamic acid tert-butyl esterYield 99%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

N-Cyclopropyl-N-piperidin-4-yl-3-trifluoromethyl-benzenesulfonamide (0.372 g, 1.1 mmol), HOBt (0.145 g, 1.1 mmol), EDCI (0.246 g, 1.32 mmol) and rac-cis-2-(tert-butoxycarbonylamino)-cyclopentanecarboxylic acid (0.275 g, 1.2 mmol) were dissolved in 5 ml of dry CH2Cl2. The mixture allowed to stir at room temperature for 12 hours. The reaction mixture was diluted with 30 ml of CHCl3 and washed with 10 ml of H2O. The organic layer was dried over MgSO4 and concentrated to dryness. The crude product was purified through a column of silica gel with a gradient of 30% to 70% EtOAc in hexane to afford the rac-((1R,2S)-2-{4-[cyclopropyl-(3-trifluoromethyl-benzenesulfonyl)-amino]-piperidine-1-carbonyl}-cyclopentyl)-carbamic acid tert-butyl ester (592 mg, 99%).

Workup

  1. washwashed with 10 ml of H2O
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated to dryness
  4. customThe crude product was purified through a column of silica gel with a gradient of 30% to 70% EtOAc in hexane

Sources & evidence

ORD record
ord-c33a251229f942d18a0444cb7caebb6a
Source dataset
uspto-grants-2015_01
Patent number
US08937181B2

Reaction notes

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