4-(Bromomethyl)-1,2-dichlorobenzene → Di-tert-butyl (1S,2R,3S,4R,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-[(3,4-dichlorobenzyl)oxy]-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylate

HRID 2172988Notes

Reaction equation

HRID 2172988 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[Cl:10])[CH2:5]Br.[C:11]([O:15][C:16]([NH:18][C@@:19]1([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[C@H:24]([OH:25])[C@H:23]([OH:26])[C@@H:22]2[C@H:20]1[C@H:21]2[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])=[O:17])([CH3:14])([CH3:13])[CH3:12]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O.C(OCC)C.[Ag]=O>[C:11]([O:15][C:16]([NH:18][C@@:19]1([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[C@H:24]([O:25][CH2:5][C:4]2[CH:7]=[CH:8][C:9]([Cl:10])=[C:2]([Cl:1])[CH:3]=2)[C@H:23]([OH:26])[C@@H:22]2[C@H:20]1[C@H:21]2[C:27]([O:29][C:30]([CH3:32])([CH3:31])[CH3:33])=[O:28])=[O:17])([CH3:14])([CH3:12])[CH3:13]

Participants

7

Reactant 2

HCID 6397264-(Bromomethyl)-1,2-dichlorobenzeneHCID 67704267HCID 67704267, compound

Product 1

HCID 86695972Di-tert-butyl (1S,2R,3S,4R,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-[(3,4-dichlorobenzyl)oxy]-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylateYield 100%

Reagents, catalysts & solvents 4

HCID 67553Tetrabutylammonium IodideCatalystHCID 92152Silver(II) oxideCatalystHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

Add 3,4-dichlorobenzyl bromide (1.02 mL, 1.02 g, 4.26 mmol) to di-tert-butyl (1S,2R,3S,4R,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3,4-dihydroxybicyclo[3.1.0]hexane-2,6-dicarboxylate (1.22 g, 2.84 mmol), tetra-n-butylammonium iodide (1.07 g, 2.84 mmol) and silver oxide (987.35 mg, 4.26 mmol) in dimethylformamide (17 mL) at room temperature. Stir overnight. Dilute with diethyl ether and hexanes (1:1), filter through celite, and then wash with ether and hexanes (1:1). The filtrate is washed with water, brine, dried over magnesium sulfate, and concentrated under reduced pressure to give a residue. The residue is purified by flash chromatography, eluting with 0-30% ethyl acetate:hexanes to give the title compound (1.7 g, 2.84 mmol, 78%): MS (m/z): 610/612 (M+Na).

Workup

  1. filtrationfilter through celite
  2. washwash with ether and hexanes (1:1)
  3. washThe filtrate is washed with water, brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customto give a residue
  7. customThe residue is purified by flash chromatography
  8. washeluting with 0-30% ethyl acetate

Sources & evidence

ORD record
ord-26f0093c1f2d4f33ad03fdb521dd37d2
Source dataset
uspto-grants-2015_06
Patent number
US09056844B2

Reaction notes

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