Tetrahydrofuran → (R)-3-(5-Methyl-3-oxo-1H-pyrrolo[1,2-c]imidazol-2(3H)-yl)-2,3-dihydro-1H-indene-5-carboxylic acid
Reaction equation
C[O:2][C:3]([C:5]1[CH:13]=[C:12]2[C:8]([CH2:9][CH2:10][C@H:11]2[NH:14][CH2:15][C:16]2[N:17]([C:21](OC(C)(C)C)=[O:22])[CH:18]=[CH:19][CH:20]=2)=[CH:7][CH:6]=1)=[O:4].[H-].[Na+].[CH2:30]1COCC1>>[CH3:30][C:18]1[N:17]2[C:21](=[O:22])[N:14]([C@H:11]3[C:12]4[C:8](=[CH:7][CH:6]=[C:5]([C:3]([OH:2])=[O:4])[CH:13]=4)[CH2:9][CH2:10]3)[CH2:15][C:16]2=[CH:20][CH:19]=1Participants
Reactant 3
Product 1
Conditions
- Temperature
- 25 °C
Procedure
A solution of (R)-tert-butyl 2-((6-(methoxycarbonyl)-2,3-dihydro-1H-inden-1-ylamino)methyl)-1H-pyrrole-1-carboxylate (500 mg, 1.3 mmol, 1.0 eq.) in THF (5 ml) was added to a stirred suspension of NaH (104 mg, 2.6 mmol, 2.0 eq., 60% in mineral oil) in THF (15 ml) at 0° C. and the resulting reaction mixture was stirred at 25° C. for 14 h. The reaction mixture was quenched with water (50 ml) and washed with ethyl acetate (50 ml). The aqueous layer was acidified with 2 N HCl (5 ml) and extracted with ethyl acetate (2×100 ml). The combined organic fractions were washed with brine (50 ml), dried over sodium sulfate and the solvent evaporated under reduced pressure. The residue obtained was used for the next step without further purification. Yield: 26% (100 mg, 0.34 mmol).
Workup
- customthe resulting reaction mixture
- customThe reaction mixture was quenched with water (50 ml)
- washwashed with ethyl acetate (50 ml)
- extractionextracted with ethyl acetate (2×100 ml)
- washThe combined organic fractions were washed with brine (50 ml)
- dry with materialdried over sodium sulfate
- customthe solvent evaporated under reduced pressure
- customThe residue obtained
- customwas used for the next step without further purification
Sources & evidence
- ORD record
- ord-d4cc32dd4c7246f0ae20a670a4b8552b
- Source dataset
- uspto-grants-2013_06
- Patent number
- US08455475B2
Reaction notes
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