Diisopropylethylamine → 1-Benzhydryl-5-bromo-1H-indole-2-carboxylic Acid

HRID 987164

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([OH:13])=[O:12])=[CH:5]2.CCN(C(C)C)C(C)C.Br[CH:24]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>CN1CCCC1=O.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH:24]([N:7]1[C:8]2[C:4](=[CH:3][C:2]([Br:1])=[CH:10][CH:9]=2)[CH:5]=[C:6]1[C:11]([OH:13])=[O:12])([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To 5-bromoindole-2-carboxylic acid (1.024 g, 4.26 mmol) in 1-methyl-2-pyrrolidinone (13 mL) at 0° C. were added iPr2NEt (25.6 mmol), tetrabutylammonium iodide (157 mg, 0.426 mmol) and bromodiphenylmethane (1.20 g, 4.86 mmol). The reaction mixture was heated at 50° C. for 21 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 (15% EtOAc in hexane) yielded 1.51 g (87% yield) of the product.

Workup

custombefore partitioning between diethyl ether and ice water
extractionthe aqueous layer was extracted with diethyl ether
washwashed with NaH2PO4
dry with materialdried over MgSO4
customevaporated to dryness
customPurification on silica gel column (15% EtOAc in hexane)

Sources & evidence

ORD record: ord-6cb4001a5be84c5788f0ca0ba350875e
Source dataset: uspto-grants-2003_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06630496B1

Linked notes

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