Tetrahydrofuran → 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

HRID 2172991Notes

Reaction equation

HRID 2172991 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[C:6]([O:10][C:11]([NH:13][C@@:14]1([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[C@H:19]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([Cl:29])[CH:23]=2)[C@H:18]([OH:30])[C@@H:17]2[C@H:15]1[C@H:16]2[C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])=[O:12])([CH3:9])([CH3:8])[CH3:7].C(N(CC)CC)C.O1CCCC1.C(=O)(O)[O-].[Na+]>>[C:6]([O:10][C:11]([NH:13][C@@:14]1([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[C@H:19]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([Cl:29])[CH:23]=2)[C@H:18]([O:30][S:2]([CH3:1])(=[O:4])=[O:3])[C@@H:17]2[C@H:15]1[C@H:16]2[C:31]([O:33][C:34]([CH3:35])([CH3:37])[CH3:36])=[O:32])=[O:12])([CH3:9])([CH3:7])[CH3:8]

Participants

6

Reactant 5

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 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-dicarboxylate

Product 1

HCID 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-dicarboxylateYield 62%

Procedure

Methanesulfonyl chloride (0.841 mL, 1.25 g, 10.87 mmol) is added to 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 (2.00 g, 3.40 mmol), triethylamine (1.66 mL, 1.20 g, 11.89 mmol), and tetrahydrofuran (33.98 mL, 30.11 g, 417.61 mmol) at 0° C. and stirred. Gradually warm the reaction to room temperature and stir overnight. Dilute the reaction with saturated aqueous sodium bicarbonate then extract with ethyl acetate (3×100 mL). The combined organic extracts are washed with brine, dried over magnesium sulfate, filtered, and then concentrated under reduced pressure to yield a residue. The residue is purified by flash chromatography using eluting with 5-60% ethyl acetate in hexanes to give the title compound (1.40 g, 2.10 mmol, 62%).

Workup

  1. temperatureGradually warm
  2. customthe reaction to room temperature
  3. stirringstir overnight
  4. additionDilute
  5. extractionthen extract with ethyl acetate (3×100 mL)
  6. washThe combined organic extracts are washed with brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto yield a residue
  11. customThe residue is purified by flash chromatography
  12. washusing eluting with 5-60% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-d590259d484348d9b649e13731edd666
Source dataset
uspto-grants-2015_06
Patent number
US09056844B2

Reaction notes

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