Nitrogen → HCID 86627067, compound

HRID 1427328Notes

Reaction equation

HRID 1427328 reaction equation
[C:1]([NH:20][C@@H:21]1[CH2:25][C@@H:24]([C:26]([OH:28])=[O:27])[CH:23]=[CH:22]1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].C([N+](CCCC)(CCCC)CCCC)CCC.N#N.[Br:49]Br.[O-]S([O-])=O.[Na+].[Na+]>C(Cl)Cl.CO.O>[Br:49][C@H:22]1[C@H:23]2[C@H:24]([C:26](=[O:28])[O:27]2)[CH2:25][C@H:21]1[NH:20][C:1]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 5

HCID 947NitrogenHCID 24408BromineHCID 24437Sodium SulfiteHCID 2723671Tetrabutylammonium HydroxideHCID 68909465HCID 68909465, compound

Product 1

HCID 86627067HCID 86627067, compoundYield 66.8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Procedure

To (1R,4R)-4-(tritylamino)cyclopent-2-ene-1-carboxylic acid (0.9 g, 0.0024360 mol) dissolved in methylene chloride (20 mL), was added 31% tetrabutylammonium hydroxide in MeOH (2.579 mL), and the mixture was stirred for 30 minutes at ambient temperature. The mixture was concentrated under reduced pressure. The resultant residue was then dissolved in methylene chloride (20 mL, 0.3 mol) and cooled to −70° C. under a blanket of N2. Bromine (251 uL, 0.00487 mol) in 5 ml of methylene chloride was then added dropwise and the mixture was stirred at −70° C. for 1 hour, then warmed to 0° C. Upon reaching 0° C., 20 mL of 5% w/v Na2SO3 in water was added dropwise and mixture was allowed to warm to ambient temperature. The reaction mixture was extracted with methylene chloride (3×10 mL), organic layers were combined and dried over Na2SO4, filtered and concentrated to give a red residue. The residue was filtered through a silica gel plug, eluting with 0 to 30% EtOAc/Hexane to remove inorganics and impurities to afford the title compound (0.73 g) as a white solid. 1H NMR (300 MHz, DMSO, δ): 7.49 (m, 6H), 7.24 (m, 9H), 4.95 (d, 1H), 3.91 (m, 1H), 3.65 (m, 1H), 2.97 (m, 1H), 2.66 (m, 1H), 1.62 (m, 1H) and 1.20 (m, 1H). LCMS: Rf=14.40 mins, ES+Na=470 (AA).

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. stirringthe mixture was stirred at −70° C. for 1 hour
  3. temperaturewarmed to 0° C
  4. customUpon reaching 0° C.
  5. additionwas added dropwise
  6. temperatureto warm to ambient temperature
  7. extractionThe reaction mixture was extracted with methylene chloride (3×10 mL), organic layers
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give a red residue
  12. filtrationThe residue was filtered through a silica gel plug
  13. washeluting with 0 to 30% EtOAc/Hexane
  14. customto remove inorganics and impurities

Sources & evidence

ORD record
ord-57bd9b335c4142eebd6234485a602483
Source dataset
uspto-grants-2015_01
Patent number
US08933225B2

Reaction notes

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