Isobutyl nitrite → Ethyl 8-bromo-7-(4-(tert-butoxycarbonyl)phenoxy)-6-chlorochroman-4-carboxylate

HRID 1021407Notes

Reaction equation

HRID 1021407 reaction equation
N(OCC(C)C)=O.N[C:9]1[CH:32]=[C:31]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH:30]=[CH:29][C:10]=1[O:11][C:12]1[C:21]([Br:22])=[C:20]2[C:15]([CH:16]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:17][CH2:18][O:19]2)=[CH:14][C:13]=1[Cl:28]>CN(C)C=O>[Br:22][C:21]1[C:12]([O:11][C:10]2[CH:9]=[CH:32][C:31]([C:33]([O:35][C:36]([CH3:37])([CH3:39])[CH3:38])=[O:34])=[CH:30][CH:29]=2)=[C:13]([Cl:28])[CH:14]=[C:15]2[C:20]=1[O:19][CH2:18][CH2:17][CH:16]2[C:23]([O:25][CH2:26][CH3:27])=[O:24]

Participants

4

Reactant 2

HCID 10958Isobutyl nitriteHCID 67080476Ethyl 7-(2-amino-4-(tert-butoxycarbonyl)phenoxy)-8-bromo-6-chlorochroman-4-carboxylate

Product 1

HCID 67080441Ethyl 8-bromo-7-(4-(tert-butoxycarbonyl)phenoxy)-6-chlorochroman-4-carboxylateYield 17%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
68 °C

Procedure

N,N-dimethylformamide (20 mL) was heated in an oil bath set to 70° C. Isobutyl nitrite (0.90 mL, 7.6 mmol) was added, and to the resulting stirred solution at 68° C. was added a solution of ethyl 7-(2-amino-4-(tert-butoxycarbonyl)phenoxy)-8-bromo-6-chlorochroman-4-carboxylate (1.6 g, 6.0 mmol) in N,N-dimethylformamide (6 mL), dropwise over 5 minutes. The resulting solution was stirred at 70° C. for 30 minutes. The resulting red solution was cooled to ambient temperature and partitioned between water (600 mL) and ethyl acetate (50 mL) The organic layer was washed with 1M hydrochloric acid (10 mL) and brine (10 mL), then dried over sodium sulfate and concentrated. The residue was purified by chromatography on silica gel, eluting with 95/5 to 85/15 hexanes/ethyl acetate, to afford ethyl 8-bromo-7-(4-(tert-butoxycarbonyl)phenoxy)-6-chlorochroman-4-carboxylate as an orange oil (0.27 g, 17% yield).

Workup

  1. customset to 70° C
  2. stirringThe resulting solution was stirred at 70° C. for 30 minutes
  3. temperatureThe resulting red solution was cooled to ambient temperature
  4. custompartitioned between water (600 mL) and ethyl acetate (50 mL) The organic layer
  5. washwas washed with 1M hydrochloric acid (10 mL) and brine (10 mL)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by chromatography on silica gel
  9. washeluting with 95/5 to 85/15 hexanes/ethyl acetate

Sources & evidence

ORD record
ord-a369fa2283474443abed04fc4586d0ef
Source dataset
uspto-grants-2014_05
Patent number
US08716498B2

Reaction notes

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