Cyclobutanecarboxylic acid → HCID 67442169, compound

HRID 1801312Notes

Reaction equation

HRID 1801312 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:17]([CH3:19])([CH3:18])[CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:20]([O:22][CH3:23])=[O:21])[CH:14]=3)[NH:9]2)=[CH:4][C:3]=1[N+:24]([O-])=O.[CH:27]1([C:31](O)=[O:32])[CH2:30][CH2:29][CH2:28]1.C(N(CC)C(C)C)(C)C.P(Cl)(Cl)(Cl)=O>ClCCl>[CH:27]1([C:31]([NH:24][C:3]2[CH:4]=[C:5]([CH:8]3[C:17]([CH3:19])([CH3:18])[CH2:16][C:15]4[C:10](=[CH:11][CH:12]=[C:13]([C:20]([O:22][CH3:23])=[O:21])[CH:14]=4)[NH:9]3)[CH:6]=[CH:7][C:2]=2[F:1])=[O:32])[CH2:30][CH2:29][CH2:28]1

Participants

6

Reactant 4

HCID 19494Cyclobutanecarboxylic acidHCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 67442620Methyl 2-(4-fluoro-3-nitrophenyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinoline-6-carboxylate

Product 1

HCID 67442169HCID 67442169, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To an ice-cold mixture of methyl 2-(4-fluoro-3-nitrophenyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinoline-6-carboxylate (0.3 mmol, 1.0 eq.), cyclobutanecarboxylic acid (0.46 mmol, 1.5 eq.), N,N-diisopropylethylamine (0.6 mmol, 2.0 eq.) in dichloromethane (5 mL) was added a solution of phosphorus oxychloride (0.36 mmol, 1.2 eq.). Then the reaction mixture was stirred at room temperature for 2.5 hours. LC-MS indicated that the starting material was consumed completely. The reaction was quenched by 20 mL water extracted with ethyl acetate (20 mL×2). The combined organic layer was concentrated and the residue was purified by column chromatography (petroleum ether/ethyl acetate=3:1) to afford methyl 2-(3-(cyclobutanecarboxamido)-4-fluorophenyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinoline-6-carboxylate as a pale yellow solid; Yield: 89%; MS (ESI+APCI) M+1=411.

Workup

  1. customwas consumed completely
  2. customThe reaction was quenched by 20 mL water
  3. extractionextracted with ethyl acetate (20 mL×2)
  4. concentrationThe combined organic layer was concentrated
  5. customthe residue was purified by column chromatography (petroleum ether/ethyl acetate=3:1)

Sources & evidence

ORD record
ord-375c829528cb47829cf8f79307af6991
Source dataset
uspto-grants-2013_01
Patent number
US08344137B2

Reaction notes

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