Fluorene-1-carboxylic acid → 1-(1-Fluorenecarbonyl)-3-(RS)-((4-phenyl)piperidin-1-yl)methyl-4-(SR)-phenylpyrrolidine

HRID 1276502Notes

Reaction equation

HRID 1276502 reaction equation
[C:1]1([CH:7]2[CH2:12][CH2:11][N:10]([CH2:13][CH:14]3[CH:18]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH2:17][NH:16][CH2:15]3)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CCN(C(C)C)C(C)C.O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1.[C:49]1([C:62](O)=[O:63])[C:61]2[CH2:60][C:59]3[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=3)[C:53]=2[CH:52]=[CH:51][CH:50]=1>C(Cl)Cl>[C:49]1([C:62]([N:16]2[CH2:17][CH:18]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:14]([CH2:13][N:10]3[CH2:9][CH2:8][CH:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[CH2:12][CH2:11]3)[CH2:15]2)=[O:63])[C:61]2[CH2:60][C:59]3[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=3)[C:53]=2[CH:52]=[CH:51][CH:50]=1

Participants

6

Reactant 4

HCID 80468Fluorene-1-carboxylic acidHCID 81531DiisopropylethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 545487023-(RS)-((4-phenyl)piperidin-1-yl)methyl-4-(SR)-phenylpyrrolidine

Product 1

HCID 702027581-(1-Fluorenecarbonyl)-3-(RS)-((4-phenyl)piperidin-1-yl)methyl-4-(SR)-phenylpyrrolidineYield 88%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 10 mg (0.03 mnmol) of 3-(RS)-((4-phenyl)piperidin-1-yl)methyl-4-(SR)-phenylpyrrolidine (from Example 30, Step A), 10 mg (0.07 mmol) of DIEA and 10 mg (0.04 mmol) of bis (2-oxo-3-oxazolidinyl)phosphinic chloride (BOP-Cl) in 2 mL of CH2Cl2 (2 mL) at 0° C. was treated with 7 mg (0.16 mmol) of 1-fluorene carboxylic acid. The cooling bath was removed; the reaction was stirred at rt for 2 h and then was concentrated in vacuo . Preparative thin layer chromatography (silica gel GF, 20×20 cm, 1000 microns) using 95:5 v/v MeOH/CH2Cl2 as the eluant afforded 14 mg (88%) of the title compound as a foam. 1H NMR (500 MHz, CDCl3): δ7.12-7.87 (17H), 1.28-4.13 (19H). Mass Spectrum (NH3 -CI): 513 (M+1).

Workup

  1. customThe cooling bath was removed
  2. concentrationwas concentrated in vacuo

Sources & evidence

ORD record
ord-0ba84158745a456f9328aa030cd3c38e
Source dataset
uspto-grants-2000_12
Patent number
US06166037

Reaction notes

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