Ethyl Acetate → Methyl 5-amino-1-bromo-indan carboxylate

HRID 507090Notes

Reaction equation

HRID 507090 reaction equation
[Br:1]N1C(=O)CCC1=O.COC([C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][C:21]=1[NH2:22])[CH2:18][CH2:17][CH2:16]2)=O.[C:23]([O:26][CH2:27]C)(=[O:25])C>C(O)(=O)C>[NH2:22][C:21]1[CH:20]=[C:19]2[C:15](=[CH:14][CH:13]=1)[C:16]([Br:1])([C:23]([O:26][CH3:27])=[O:25])[CH2:17][CH2:18]2

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 67184N-bromobutanimideHCID 59379136methyl 6-amino-2,3-dihydro-1H-indene-5-carboxylate

Product 1

HCID 67422511Methyl 5-amino-1-bromo-indan carboxylateYield 95%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Add N-bromosuccinimide (1.87 g, 10.5 mmol) to methyl 6-amino-indan-5-carboxylate (1.82 g, 9.53 mmol) (Example 49, Step 3) in acetic acid (9.3 mL). Stir the mixture at room temperature for 1 h. Pour the mixture into ice water and add ethyl acetate. Separate the layers and wash the organic phase with saturated NaHCO3 and brine and dry over sodium sulfate. Remove the solvent under reduced pressure. Purify with silica gel cartridge, eluting with hexanes/ethyl acetate to afford methyl 5-amino-1-bromo-indan carboxylate (2.45 g, 95%): MS (ES+): 271, 272 (M+H). Add methyl boronic acid (1.6 g, 26.7 mmol), cesium fluoride (4.6 g, 30.22 mmol) and 1-bis(diphenylphosphinoferrocene) palladium chloride (727 mg, 0.89 mmol) to methyl 5-amino-1-bromo-indan carboxylate (2.40 g, 8.89 mmol) in dioxane (60 ml), and stir at 90° C. for 12 h. Partition between water and ethyl acetate. Extract with more ethyl acetate and then combine the organic phases. Dry over sodium sulfate and remove the solvent under reduced pressure. Purify with silica gel cartridge, eluting with hexanes/ethyl acetate to afford the titled compound (1.73 g, 95%). MS (ES+): 206 (M+H).

Workup

  1. customSeparate the layers
  2. washwash the organic phase with saturated NaHCO3 and brine
  3. dry with materialdry over sodium sulfate
  4. customRemove the solvent under reduced pressure
  5. customPurify with silica gel cartridge
  6. washeluting with hexanes/ethyl acetate

Sources & evidence

ORD record
ord-55be49a00df34ecbbf468c78df5e63a5
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

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