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Sodium Carbonate → 1-(3,5-Dichloro-4'-fluoro-biphenyl-4-ylmethyl)-3-(4-methoxy-cyclohexyl)-pyrrolidin-2-one

HRID 1670835
Notes
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Reaction equation

HRID 1670835 reaction equation
Br[C:2]1[CH:22]=[C:21]([Cl:23])[C:5]([CH2:6][N:7]2[CH2:11][CH2:10][CH:9]([CH:12]3[CH2:17][CH2:16][CH:15]([O:18][CH3:19])[CH2:14][CH2:13]3)[C:8]2=[O:20])=[C:4]([Cl:24])[CH:3]=1.[F:25][C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1.O.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:24][C:4]1[CH:3]=[C:2]([C:29]2[CH:30]=[CH:31][C:26]([F:25])=[CH:27][CH:28]=2)[CH:22]=[C:21]([Cl:23])[C:5]=1[CH2:6][N:7]1[CH2:11][CH2:10][CH:9]([CH:12]2[CH2:17][CH2:16][CH:15]([O:18][CH3:19])[CH2:14][CH2:13]2)[C:8]1=[O:20]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 673556821-(4-Bromo-2,6-dichloro-benzyl)-3-(4-methoxy-cyclohexyl)-pyrrolidin-2-one

Product 1

HCID 673562951-(3,5-Dichloro-4'-fluoro-biphenyl-4-ylmethyl)-3-(4-methoxy-cyclohexyl)-pyrrolidin-2-oneYield 108.6%

Reagents, catalysts & solvents 4

HCID 178418397
HCID 178418397, compound
Catalyst
HCID 962WaterSolvent
HCID 8028TetrahydrofuranSolvent
HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 1-(4-Bromo-2,6-dichloro-benzyl)-3-(4-methoxy-cyclohexyl)-pyrrolidin-2-one (0.4 g, 0.92 mmol) and 4-fluorophenylboronic acid (0.19 g, 1.38 mmol) in THF (15 mL) and water (5 mL) and sodium carbonate (0.29, 0.75 g) is purged with N2. Treat the reaction with Pd(PPh3)4 (0.05 g, 0.046 mmol) and heat to 80° C. for 2 hour under N2. Cool the reaction, dilute with ethyl acetate, and wash with HCl (1N) and water. Dry the organic layer (Na2SO4), remove the solvent in vacuo to afford crude product, and purify with a 35% ethyl acetate in hexanes to afford 0.45 g of the titled product. MS (m/z): 451 (M+).

Workup

  1. customis purged with N2
  2. additionTreat
  3. temperatureCool
  4. customthe reaction
  5. washwash with HCl (1N) and water
  6. dry with materialDry the organic layer (Na2SO4)
  7. customremove the solvent in vacuo
  8. customto afford crude product
  9. custompurify with a 35% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-975f527875ca4ec8bd91b2c1d6dc0e15
Source dataset
uspto-grants-2011_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07994176B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes