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

HRID 2172994Notes

Reaction equation

HRID 2172994 reaction equation
[N-:1]=[N+:2]=[N-:3].[Na+].[C:5]([O:9][C:10]([NH:12][C@@:13]1([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[C@H:18]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([Cl:28])[CH:22]=2)[C@H:17](OS(C)(=O)=O)[C@@H:16]2[C@H:14]1[C@H:15]2[C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])=[O:11])([CH3:8])([CH3:7])[CH3:6].C1OCCOCCOCCOCCOC1.CN(C)C=O>O>[N:1]([C@H:17]1[C@@H:16]2[C@@H:14]([C@H:15]2[C:34]([O:36][C:37]([CH3:38])([CH3:39])[CH3:40])=[O:35])[C@:13]([NH:12][C:10]([O:9][C:5]([CH3:6])([CH3:7])[CH3:8])=[O:11])([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[C@@H:18]1[O:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([Cl:28])[CH:22]=1)=[N+:2]=[N-:3]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 33557Sodium AzideHCID 3633615-Crown-5HCID 86695975Di-tert-butyl (1S,2R,3S,4R,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-[(3,4-dichlorobenzyl)oxy]-4-[(methylsulfonyl)oxy]bicyclo[3.1.0]hexane-2,6-dicarboxylate

Product 1

HCID 86695978Di-tert-butyl (1S,2R,3R,4S,5R,6S)-4-azido-2-[(tert-butoxycarbonyl)amino]-3-[(3,4-dichlorobenzyl)oxy]bicyclo[3.1.0]hexane-2,6-dicarboxylateYield 72%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Sodium azide (8.29 g, 127.45 mmol) is added to di-tert-butyl (1S,2R,3S,4R,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-[(3,4-dichlorobenzyl)oxy]-4-[(methylsulfonyl)oxy]bicyclo[3.1.0]hexane-2,6-dicarboxylate (16.99 g, 25.49 mmol) and 15-crown-5 (508.57 μL, 561.46 mg, 2.55 mmol) in dimethylformamide (254.90 mL, 240.96 g, 3.30 moles) at 85° C. and stirred. After 7 days, the reaction is cooled to room temperature then diluted with water and extracted with ethyl acetate (3×). The combined organics are washed with water, brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure giving a residue. The residue is purified by flash chromatography eluting 2-60% ethyl acetate in hexanes to yield the title compound (11.2 g, 18.3 mmol, 72%). MS (m/z): 635/637 (M+1).

Workup

  1. extractionextracted with ethyl acetate (3×)
  2. washThe combined organics are washed with water, brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customgiving a residue
  7. customThe residue is purified by flash chromatography
  8. washeluting 2-60% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-29ba30a4179844f58cfbed581fc3d2eb
Source dataset
uspto-grants-2015_06
Patent number
US09056844B2

Reaction notes

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