4-Methylmorpholine → (R)-3-[3,5-dichloro-4'-(4-trifluoromethyl-piperidine-1-carbonyl)-biphenyl-4-ylmethyl]-1-(tetrahydro-pyran-4-yl)-pyrrolidin-2-one

HRID 416021Notes

Reaction equation

HRID 416021 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:22]2[CH:27]=[CH:26][C:25]([C:28]([OH:30])=O)=[CH:24][CH:23]=2)[CH:5]=[C:6]([Cl:21])[C:7]=1[CH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([CH:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:10]1=[O:20].Cl.[F:32][C:33]([F:41])([F:40])[CH:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1.ON1C2C=CC=CC=2N=N1.CN1CCOCC1.CCN=C=NCCCN(C)C.Cl>ClCCl>[Cl:21][C:6]1[CH:5]=[C:4]([C:22]2[CH:27]=[CH:26][C:25]([C:28]([N:37]3[CH2:38][CH2:39][CH:34]([C:33]([F:41])([F:40])[F:32])[CH2:35][CH2:36]3)=[O:30])=[CH:24][CH:23]=2)[CH:3]=[C:2]([Cl:1])[C:7]=1[CH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([CH:14]2[CH2:15][CH2:16][O:17][CH2:18][CH2:19]2)[C:10]1=[O:20]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 162181604-(Trifluoromethyl)piperidine hydrochlorideHCID 66621883HCID 66621883, compound

Product 1

HCID 24757987(R)-3-[3,5-dichloro-4'-(4-trifluoromethyl-piperidine-1-carbonyl)-biphenyl-4-ylmethyl]-1-(tetrahydro-pyran-4-yl)-pyrrolidin-2-oneYield 72%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Treat a solution of 3′,5′-dichloro-4′-[(R)-2-oxo-1-(tetrahydro-pyran-4-yl)-pyrrolidin-3-ylmethyl]-biphenyl-4-carboxylic acid (0.25 g, 0.56 mmol), 4-(trifluoromethyl)piperidine hydrochloride (0.13 g, 0.67 mmol), 1-hydroxybenzotriazole (0.23 g, 0.67 mmol), and 4-methylmorpholine (0.18 mL, 1.67 mmol) in dichloromethane (10 mL) with N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (0.13 g, 0.67 mmol) and stir at room temperature for 6 hr. Quench the reaction with 1N hydrochloric acid and extract with ethyl acetate. Wash the organic layer with brine, dry over magnesium sulfate, and filter. Purify the crude material by silica gel column chromatography using hexanes:ethyl acetate to afford 0.23 g (72%) of desired product: MS (m/z): 583 (M+).

Workup

  1. customQuench
  2. customthe reaction with 1N hydrochloric acid
  3. extractionextract with ethyl acetate
  4. washWash the organic layer with brine
  5. dry with materialdry over magnesium sulfate
  6. filtrationfilter
  7. customPurify the crude material by silica gel column chromatography

Sources & evidence

ORD record
ord-34d55f94c3c741b7b5464b90ddd3223d
Source dataset
uspto-grants-2012_01
Patent number
US08088776B2

Reaction notes

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