Bromomethylcyclopropane → 2-[5-bromo-1-(cyclopropylmethyl)-1H-indol-3-yl]acetic acid

HRID 2301661Notes

Reaction equation

HRID 2301661 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][C:12]([OH:14])=[O:13].CCN(C(C)C)C(C)C.Br[CH2:25][CH:26]1[CH2:28][CH2:27]1>CN1CCCC1=O>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:25][CH:26]1[CH2:28][CH2:27]1)[CH:6]=[C:5]2[CH2:11][C:12]([OH:14])=[O:13]

Participants

5

Reactant 3

HCID 81503BromomethylcyclopropaneHCID 81531DiisopropylethylamineHCID 967345-Bromo-3-indoleacetic acid

Product 1

HCID 183733592-[5-bromo-1-(cyclopropylmethyl)-1H-indol-3-yl]acetic acidYield 86%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
50 °C

Procedure

To 5-bromoindole-3-acetic acid (890 mg, 3.5 mmol) in 1-methyl-2-pyrrolidinone (12 mL) at 0° C. were added iPr2NEt (21 mmol) and bromomethylcyclopropane (10.5 mmol). The reaction mixture was heated at 50° C. for 19 h before partitioning between diethyl ether and ice water. After adjusting the pH to 3, the aqueous layer was extracted with diethyl ether. The organic layers were combined, washed with NaH2PO4, dried over MgSO4 and evaporated to dryness. Purification on silica gel column (30% EtOAc in hexane) yielded 927 mg (86% yield) of the product.

Workup

  1. custombefore partitioning between diethyl ether and ice water
  2. extractionthe aqueous layer was extracted with diethyl ether
  3. washwashed with NaH2PO4
  4. dry with materialdried over MgSO4
  5. customevaporated to dryness
  6. customPurification on silica gel column (30% EtOAc in hexane)

Sources & evidence

ORD record
ord-959633b3027f4cc982c7050e9202a921
Source dataset
uspto-grants-2002_12
Patent number
US06500853B1

Reaction notes

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