Toluene → HCID 68551030, compound

HRID 1868124Notes

Reaction equation

HRID 1868124 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([S:12]([N:15]2[CH2:20][CH2:19][N:18]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:22]=3[C:28]([F:31])([F:30])[F:29])[CH2:17][C@H:16]2[CH3:32])(=[O:14])=[O:13])=[CH:4][CH:3]=1.[C:33]([O:37][C:38]([N:40]1[CH2:45][CH2:44][N:43](C)[CH2:42][CH2:41]1)=[O:39])([CH3:36])([CH3:35])[CH3:34].CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1>ClCCl.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:27][C:24]1[CH:25]=[CH:26][C:21]([N:18]2[CH2:19][CH2:20][N:15]([S:12]([C:5]3[C:6]4[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=4)[C:2]([N:43]4[CH2:42][CH2:41][N:40]([C:38]([O:37][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:39])[CH2:45][CH2:44]4)=[CH:3][CH:4]=3)(=[O:14])=[O:13])[C@H:16]([CH3:32])[CH2:17]2)=[C:22]([C:28]([F:31])([F:30])[F:29])[CH:23]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 114013941-Boc-4-methylpiperazineHCID 23676156Sodium t-butoxideHCID 68553410HCID 68553410, compound

Product 1

HCID 68551030HCID 68551030, compoundYield 66.9%

Reagents, catalysts & solvents 2

HCID 634876Binap, (A+-)-CatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of (2R)-1-[(4-bromo-1-naphthyl)sulfonyl]-4-[4-fluoro-2-(trifluoromethyl)phenyl]-2-methylpiperazine (250 mg, 0.47 mmol), 4-methyl-piperazine-1-carboxylic acid tert-butyl ester (175.1 mg, 0.94 mmol), tris(dibenzylidineacetone)dipalladium (0) (4.3 mg, 0.0047 mmol), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphtyl (8.78 mg, 0.014 mmol) and sodium tert-butoxide (56.5 mg, 0.59 mmol) were charged to a microwave vial. Toluene (3.0 mL) was introduced under nitrogen atmosphere and the reaction mixture was irradiated at 110° C. for 35 minutes. Reaction was complete as determined by TLC. Reaction mixtures was diluted with dichloromethane, washed with water, saturated brine then dried over Na2SO4 and concentrated. The crude product was purified via flash column chromatography to yield tert-butyl 4-[4-({(2R)-4-[4-fluoro-2-(trifluoromethyl)phenyl]-2-methylpiperazin-1-yl}sulfonyl)-1-naphthyl]piperazine-1-carboxylate as yellow gum (200.1 mg, 66.9% yield).

Workup

  1. additionwere charged to a microwave vial
  2. customthe reaction mixture was irradiated at 110° C. for 35 minutes
  3. customReaction
  4. customReaction mixtures
  5. washwashed with water, saturated brine
  6. dry with materialthen dried over Na2SO4
  7. concentrationconcentrated
  8. customThe crude product was purified via flash column chromatography

Sources & evidence

ORD record
ord-128c581446864681b048a4bf4fb1b4b4
Source dataset
uspto-grants-2009_12
Patent number
US07632838B2

Reaction notes

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