Morpholine → (R)-3-[3,5-Dichloro-4'-(morpholine-4-carbonyl)-biphenyl-4-ylmethyl]-1-(4-triisopropylsilanyloxy-piperidin-1-yl)-pyrrolidin-2-one

HRID 1692087Notes

Reaction equation

HRID 1692087 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:33]2[CH:38]=[CH:37][C:36]([C:39]([OH:41])=O)=[CH:35][CH:34]=2)[CH:5]=[C:6]([Cl:32])[C:7]=1[CH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([N:14]2[CH2:19][CH2:18][CH:17]([O:20][Si:21]([CH:28]([CH3:30])[CH3:29])([CH:25]([CH3:27])[CH3:26])[CH:22]([CH3:24])[CH3:23])[CH2:16][CH2:15]2)[C:10]1=[O:31].C(N1C=CN=C1)(N1C=CN=C1)=O.[NH:54]1[CH2:59][CH2:58][O:57][CH2:56][CH2:55]1.C(OCC)(=O)C>C(Cl)Cl>[Cl:32][C:6]1[CH:5]=[C:4]([C:33]2[CH:34]=[CH:35][C:36]([C:39]([N:54]3[CH2:59][CH2:58][O:57][CH2:56][CH2:55]3)=[O:41])=[CH:37][CH:38]=2)[CH:3]=[C:2]([Cl:1])[C:7]=1[CH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([N:14]2[CH2:15][CH2:16][CH:17]([O:20][Si:21]([CH:25]([CH3:26])[CH3:27])([CH:22]([CH3:24])[CH3:23])[CH:28]([CH3:29])[CH3:30])[CH2:18][CH2:19]2)[C:10]1=[O:31]

Participants

6

Reactant 4

HCID 8083MorpholineHCID 8857Ethyl AcetateHCID 682631,1'-CarbonyldiimidazoleHCID 66904943(R)-3',5'-Dichloro-4'-[2-oxo-1-(4-triisopropylsilanyloxy-piperidin-1-yl)-pyrrolidin-3-ylmethyl]-biphenyl-4-carboxylic Acid

Product 1

HCID 66905099(R)-3-[3,5-Dichloro-4'-(morpholine-4-carbonyl)-biphenyl-4-ylmethyl]-1-(4-triisopropylsilanyloxy-piperidin-1-yl)-pyrrolidin-2-oneYield 90.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Treat a solution of (R)-3′,5′-dichloro-4′-[2-oxo-1-(4-triisopropylsilanyloxy-piperidin-1-yl)-pyrrolidin-3-ylmethyl]-biphenyl-4-carboxylic acid (0.2 g, 0.32 mmol) in CH2Cl2 (15 mL) with 1,1′-carbonyldiimidazole (0.10 g, 0.65 mmol) and stir for 1 hour at room temperature. Treat the reaction with morpholine (0.06 g, 0.65 mmol) and stir for 12 hours at room temperature. Load the mixture on silica gel column and flash with 25% to 35% ethyl acetate in hexanes to afford 0.20 g (90%) of the title compound. MS (m/z): 688 (M+).

Workup

  1. additionTreat
  2. stirringstir for 12 hours at room temperature

Sources & evidence

ORD record
ord-c9e1bff92b4f4dafb2798003a8864fe0
Source dataset
uspto-grants-2012_04
Patent number
US08153807B2

Reaction notes

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