Binap, (A+-)- → HCID 67367138, compound

HRID 1173066Notes

Reaction equation

HRID 1173066 reaction equation
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.Br[C:48]1[CH:53]=[CH:52][C:51]([S:54]([NH:57][C:58]2[CH:63]=[CH:62][C:61]([C@@H:64]3[CH2:70][C@@H:69]4[C@H:65]3[CH2:66][N:67]([CH2:71][CH2:72][CH3:73])[CH2:68]4)=[CH:60][CH:59]=2)(=[O:56])=[O:55])=[CH:50][CH:49]=1.[CH3:74][O:75][CH2:76][C@H:77]1[CH2:81][CH2:80][CH2:79][NH:78]1.ClCCl.CO>O1CCCC1>[CH3:74][O:75][CH2:76][C@H:77]1[CH2:81][CH2:80][CH2:79][N:78]1[C:48]1[CH:53]=[CH:52][C:51]([S:54]([NH:57][C:58]2[CH:63]=[CH:62][C:61]([C@@H:64]3[CH2:70][C@@H:69]4[C@H:65]3[CH2:66][N:67]([CH2:71][CH2:72][CH3:73])[CH2:68]4)=[CH:60][CH:59]=2)(=[O:56])=[O:55])=[CH:50][CH:49]=1

Participants

6

Reactant 4

HCID 634876Binap, (A+-)-HCID 671216(2R)-2-(Methoxymethyl)pyrrolidine2×HCID 21226129Dichloromethane methanolHCID 67365915HCID 67365915, compound

Product 1

HCID 67367138HCID 67367138, compoundYield 18%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 0.07 g rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (BINAP, 0.11 mmol) and 0.043 g tri(dibenzylideneacetone)dipalladioum(0) (0.05 mmol) in 5 ml tetrahydrofuran were added dropwise to a solution of 4-bromo-N-[4-((1R,5S,6R)-3-propyl-3-aza-bicyclo[3.2.0]hept-6-yl)-phenyl]-benzenesulfonamide (0.26 g, 0.59 mmol), (R)-2-(methoxymethyl)pyrrolidine (104 mg, 0.9 mmol), and 0.104 g sodium tert.butylate (1.08 mmol) in 20 ml tetrahydrofuran. The reaction mixture was refluxed for 5½ hours, and, after additional addition of 0.04 ml (R)-2-(methoxymethyl)pyrrolidine, for another 2 hours. After evaporation, the residue was treated with water, extracted twice with diethyl ether and dichloromethane each, and the combined organic layers dried over magnesium sulfate, filtered, and the solvent evaporated. Purification of the thus obtained crude product via silica gel chromatography using a gradient of dichloromethane/methanol 0-12% gave 50 mg (yield 18%) of the title compound.

Workup

  1. temperatureThe reaction mixture was refluxed for 5½ hours
  2. customAfter evaporation
  3. additionthe residue was treated with water
  4. extractionextracted twice with diethyl ether and dichloromethane each, and the combined organic layers
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customthe solvent evaporated
  8. customPurification of the
  9. customthus obtained crude product via silica gel chromatography

Sources & evidence

ORD record
ord-265b458b303c40ed885ba9b763267353
Source dataset
uspto-grants-2010_11
Patent number
US07834048B2

Reaction notes

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