Pyridine → HCID 66628528, compound

HRID 2380848Notes

Reaction equation

HRID 2380848 reaction equation
N1C=CC=CC=1.[Cl:7][C:8]1[CH:9]=[C:10]([CH:13]=[CH:14][C:15]=1[Cl:16])[CH2:11]Br.[CH2:17]([O:19][C:20]([C@:22]1([NH:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[C@H:27]([NH2:28])[CH2:26][C@@H:25]2[C@H:23]1[C@@:24]2([F:34])[C:29]([O:31][CH2:32][CH3:33])=[O:30])=[O:21])[CH3:18].[Cl-].[Na+]>C(Cl)(Cl)Cl>[CH2:17]([O:19][C:20]([C@:22]1([NH:35][C:36]([O:38][C:39]([CH3:41])([CH3:40])[CH3:42])=[O:37])[C@H:27]([NH:28][CH2:11][C:10]2[CH:13]=[CH:14][C:15]([Cl:16])=[C:8]([Cl:7])[CH:9]=2)[CH2:26][C@@H:25]2[C@H:23]1[C@@:24]2([F:34])[C:29]([O:31][CH2:32][CH3:33])=[O:30])=[O:21])[CH3:18]

Participants

6

Reactant 4

HCID 1049PyridineHCID 5234Sodium ChlorideHCID 6397264-(Bromomethyl)-1,2-dichlorobenzeneHCID 66628652HCID 66628652, compound

Product 1

HCID 66628528HCID 66628528, compoundYield 39.3%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

42 μL of pyridine and 123 mg of 3,4-dichlorobenzylbromide were added to 175 mg of (1R,2R,3R,5R,6R)-3-amino-2-t-butoxycarbonylamino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid diethyl ester dissolved in 0.88 mL of chloroform at ice-cooling, and the mixture was stirred for 3 days at room temperature. A saturated aqueous solution of sodium chloride was added thereto, and the mixture was extracted five times with chloroform. The organic layers were combined and then dried over anhydrous sodium sulfate. After the desiccant was filtered off, the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (silica gel: Wako gel C200, eluent:chloroform-ethanol=100:1 to 50:1, followed by hexane-ethyl acetate=5:1), thereby yielding 98 mg of (1R,2R,3R,5R,6R)-2-t-butoxycarbonylamino-3-(3,4-dichlorobenzylamino)-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid diethyl ester.

Workup

  1. temperaturecooling
  2. extractionthe mixture was extracted five times with chloroform
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationAfter the desiccant was filtered off
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe residue was purified by column chromatography (silica gel: Wako gel C200, eluent:chloroform-ethanol=100:1 to 50:1, followed by hexane-ethyl acetate=5:1)

Sources & evidence

ORD record
ord-d54321262bb04fd78cdde77e25b546e8
Source dataset
uspto-grants-2012_09
Patent number
US08258133B2

Reaction notes

Loading…