Water → Ethyl 7-(4-(tert-butoxycarbonyl)phenoxy)-6,8-dichlorochroman-4-carboxylate

HRID 1048052Notes

Reaction equation

HRID 1048052 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]([Cl: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].O>CN(C=O)C>[C:36]([O:35][C:33]([C:31]1[CH:32]=[CH:9][C:10]([O:11][C:12]2[C:21]([Cl:22])=[C:20]3[C:15]([CH:16]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:17][CH2:18][O:19]3)=[CH:14][C:13]=2[Cl:28])=[CH:29][CH:30]=1)=[O:34])([CH3:37])([CH3:38])[CH3:39]

Participants

5

Reactant 3

HCID 962WaterHCID 10958Isobutyl nitriteHCID 67080422Ethyl 7-(2-amino-4-(tert-butoxycarbonyl)phenoxy)-6,8-dichlorochroman-4-carboxylate

Product 1

HCID 67080347Ethyl 7-(4-(tert-butoxycarbonyl)phenoxy)-6,8-dichlorochroman-4-carboxylateYield 92.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
70 °C

Procedure

To a 2 L four neck round bottomed flask equipped with a thermocouple, a condenser, and an addition funnel were added DMF (200 ml) and isobutyl nitrite (30.8 ml, 260 mmol). The mixture was heated to 70° C. To the preheated mixture was added a solution of ethyl 7-(2-amino-4-(tert-butoxycarbonyl)phenoxy)-6,8-dichlorochroman-4-carboxylate (50.2 g, 104 mmol) in DMF (200 ml) over a period of 15 minutes. The reaction was slightly exothermic and gas evolution was observed. The mixture was stirred at 70° C. for 1.5 hours and cooled to ambient temperature. The mixture was transferred to a separatory funnel containing 2 liters of water. The mixture was extracted with EtOAc (500 ml, 2×250 ml). The combined extracts were washed with water (500 ml, 2×250 ml) and brine (250 ml), dried over MgSO4, filtered, and concentrated. The residue was purified on silica gel (EtOAc in hexanes gradient) to provide 45.1 g of the title compound as a very viscous oil (93%).

Workup

  1. temperaturecooled to ambient temperature
  2. customThe mixture was transferred to a separatory funnel
  3. extractionThe mixture was extracted with EtOAc (500 ml, 2×250 ml)
  4. washThe combined extracts were washed with water (500 ml, 2×250 ml) and brine (250 ml)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified on silica gel (EtOAc in hexanes gradient)

Sources & evidence

ORD record
ord-b8f3cbb49def44d4bbe499495078752a
Source dataset
uspto-grants-2013_10
Patent number
US08569522B2

Reaction notes

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