Pyridine, hydrobromide (1:1) → tert-butyl trans-10-[(tert-butoxycarbonyl)oxy]-1,3,3a,4,5,10b-hexahydro-2H-[1]benzoxepino[4,5-c]pyrrole-2-carboxylate

HRID 84968Notes

Reaction equation

HRID 84968 reaction equation
COC1[C:8]2[C@H:9]3[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:11][C@@H:10]3[CH2:21][CH2:22][O:23][C:7]=2[CH:6]=[CH:5][CH:4]=1.Br.N1C=CC=CC=1.[C:31]([O:38][C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])(OC(C)(C)C)=O>O>[C:42]([O:41][C:39]([O:38][C:31]1[C:8]2[C@H:9]3[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:18])[CH3:19])=[O:15])[CH2:11][C@@H:10]3[CH2:21][CH2:22][O:23][C:7]=2[CH:6]=[CH:5][CH:4]=1)=[O:40])([CH3:43])([CH3:44])[CH3:45]

Participants

5

Reactant 3

HCID 87810Pyridine, hydrobromide (1:1)HCID 90495Di-tert-butyl dicarbonateHCID 67167490HCID 67167490, compound

Product 1

HCID 67167836tert-butyl trans-10-[(tert-butoxycarbonyl)oxy]-1,3,3a,4,5,10b-hexahydro-2H-[1]benzoxepino[4,5-c]pyrrole-2-carboxylate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of Example 272E (2.0 g, 6.3 mmol) and pyridine-HBr (8.0 g, 50 mmol) was heated at 135° C. for 72 hours. The mixture was cooled to room temperature, water was added, and saturated NaHCO3(aqueous) was added to adjust the pH value to 7. Di-tert-butyl dicarbonate (3.0 g, 13.8 mmol) was added, and the mixture was stirred for 16 hours. The reaction mixture was extracted with ethyl acetate, dried, and concentrated. The mixture was purified by silica gel column chromatography eluting with hexanes and ethyl acetate (5:1) to give a mixture of Example 374A and tert-butyl trans-10-[(tert-butoxycarbonyl)oxy]-1,3,3a,4,5,10b-hexahydro-2H-[1]benzoxepino[4,5-c]pyrrole-2-carboxylate side product. The mixture was dissolved in methanol (10 mL) and sodium methoxide (25%, 1.5 mL) was added. The mixture was heated at 50° C. for 1 hour, 1 N HCl(aq) was added to adjust pH value to 2, and the mixture was extracted with ethyl acetate. The crude material was triturated in acetone, precipitates were collected to afford the titled compound.

Workup

  1. extractionThe reaction mixture was extracted with ethyl acetate
  2. customdried
  3. concentrationconcentrated
  4. customThe mixture was purified by silica gel column chromatography
  5. washeluting with hexanes and ethyl acetate (5:1)

Sources & evidence

ORD record
ord-6dff56ed3fe74068a3e51c326bac322e
Source dataset
uspto-grants-2014_09
Patent number
US08846951B2

Reaction notes

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