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

HRID 559308Notes

Reaction equation

HRID 559308 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([C:12]([OH:14])=O)[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:36][C:37]1[CH:38]=[C:39]([CH:44]2[CH2:48][NH:47][CH2:46][CH:45]2[CH:49]([O:51][C:52]2[CH:59]=[CH:58][C:55]([C:56]#[N:57])=[CH:54][N:53]=2)[CH3:50])[CH:40]=[CH:41][C:42]=1[Cl:43]>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH:10]([C:12]([N:47]2[CH2:48][C@H:44]([C:39]3[CH:40]=[CH:41][C:42]([Cl:43])=[C:37]([Cl:36])[CH:38]=3)[C@@H:45]([C@@H:49]([O:51][C:52]3[CH:59]=[CH:58][C:55]([C:56]#[N:57])=[CH:54][N:53]=3)[CH3:50])[CH2:46]2)=[O:14])[CH2:11]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27559811-Boc-Azetidine-3-carboxylic acidHCID 669997186-{(SR)-1-[(3RS,4SR)-4-(3,4-Dichloro-phenyl)-pyrrolidin-3-yl]-ethoxy}-nicotinonitrile

Product 1

HCID 579997493-[(3R,4S)-3-[(S)-1-(5-Cyano-pyridin-2-yloxy)-ethyl]-4-(3,4-dichloro-phenyl)-pyrrolidine-1-carbonyl]-azetidine-1-carboxylic acid tert-butyl esterYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of azetidine-1,3-dicarboxylic acid mono-tert-butyl ester (0.072 g, 0.36 mmol) in 15 mL of CH2Cl2 was added (0.069 g, 0.36 mmol) of EDC, (0.048 g, 0.36 mmol) of HOBt and Et3N (0.06 mL, 0.42 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, 0.10 g, 0.27 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 0.14 g (98%) of the title compound as a white solid.

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-008fc2c91edb40dc847e856a422858c0
Source dataset
uspto-grants-2011_11
Patent number
US08063075B2

Reaction notes

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