1,2-Dichloroethane → 4-[(3RS,4SR)-3-[(SR)-1-(5-Cyano-pyridin-2-yloxy)-ethyl]-4-(3,4-dichloro-phenyl)-pyrrolidine-1-carbonyl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 559301Notes

Reaction equation

HRID 559301 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(CC)CC.[Cl:38][C:39]1[CH:40]=[C:41]([CH:46]2[CH2:50][NH:49][CH2:48][CH:47]2[CH:51]([O:53][C:54]2[CH:61]=[CH:60][C:57]([C:58]#[N:59])=[CH:56][N:55]=2)[CH3:52])[CH:42]=[CH:43][C:44]=1[Cl:45]>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([C:14]([N:49]2[CH2:50][CH:46]([C:41]3[CH:42]=[CH:43][C:44]([Cl:45])=[C:39]([Cl:38])[CH:40]=3)[CH:47]([CH:51]([O:53][C:54]3[CH:61]=[CH:60][C:57]([C:58]#[N:59])=[CH:56][N:55]=3)[CH3:52])[CH2:48]2)=[O:16])[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 669997186-{(SR)-1-[(3RS,4SR)-4-(3,4-Dichloro-phenyl)-pyrrolidin-3-yl]-ethoxy}-nicotinonitrile

Product 1

HCID 669996164-[(3RS,4SR)-3-[(SR)-1-(5-Cyano-pyridin-2-yloxy)-ethyl]-4-(3,4-dichloro-phenyl)-pyrrolidine-1-carbonyl]-piperidine-1-carboxylic acid tert-butyl esterYield 91%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of piperidine-1,4-dicarboxylic acid mono-tert-butyl ester (0.165 g, 0.72 mmol) in 20 mL of CH2Cl2 was added (0.14 g, 0.94 mmol) of EDC, (0.10 g, 0.94 mmol) of HOBt and Et3N (0.11 mL, 1.1 mmol). After one hour at RT, was added 6-{(SR)-1-[(3RS,4SR)-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethoxy}-nicotinonitrile (VII-B-2, 0.26 g, 0.72 mmol). The mixture was stirred at RT over night and then poured onto water and extracted with CH2Cl2. The combined organic phases were dried over Na2SO4 and concentrated under vacuo. Column chromatography (SiO2, EtOAc/H, 1:1) yielded 0.29 g (91%) of the title compound as a white foam. ES-MS m/e: 574.8 (M+H+).

Workup

  1. additionpoured onto water
  2. extractionextracted with CH2Cl2
  3. dry with materialThe combined organic phases were dried over Na2SO4
  4. concentrationconcentrated under vacuo

Sources & evidence

ORD record
ord-e690d600f44f4f848ba663d960604808
Source dataset
uspto-grants-2011_11
Patent number
US08063075B2

Reaction notes

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