18-Crown-6 → HCID 9850769, compound

HRID 380510Notes

Reaction equation

HRID 380510 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[C:10]([N:12]2[CH2:16][C@@H:15]([C:17]3[CH:21]=[CH:20][S:19][CH:18]=3)[C@H:14]([CH2:22][N:23]3[CH2:28][CH2:27][CH:26]([C:29]4[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=4)[CH2:25][CH2:24]3)[CH2:13]2)=[O:11])[CH:3]=[CH:2]1.C1OCCOCCOCCOCCOCCOC1.CC(C)([O-])C.[K+].[CH3:60][O:61][C:62](=[O:65])[CH2:63]Br>CCOCC.C(Cl)Cl>[C:62]([CH2:63][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[C:10]([N:12]2[CH2:16][C@@H:15]([C:17]3[CH:21]=[CH:20][S:19][CH:18]=3)[C@H:14]([CH2:22][N:23]3[CH2:28][CH2:27][CH:26]([C:29]4[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=4)[CH2:25][CH2:24]3)[CH2:13]2)=[O:11])[CH:3]=[CH:2]1)([O:61][CH3:60])=[O:65]

Participants

7

Reactant 4

HCID 2855718-Crown-6HCID 60984Methyl bromoacetateHCID 20694306HCID 20694306, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 9850769HCID 9850769, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of 0.126 g (0.258 mmol) of 1-(7-indolecarbonyl)-3-(R)-(4-(4-fluorophenyl)piperidinylmethyl)-4-(R)-(3-thienyl)pyrrolidine in 6 mL of ether was added 0.082 g (0.31 mmol) of 18-crown-6 and 0.31 mL (0.31 mmol) of potassium t-butoxide (1M in t-BuOH). After stirring the reaction mixture at rt for 15 min, the reaction mixture was cooled to 0° C. and to it was added 0.034 mL (0.36 mmol) of methyl-2-bromoacetate. The reaction mixture was stirred at rt for 2 h. The reaction mixture was diluted with CH2Cl2 and washed with sat. NaHCO3 solution. The organic fraction was dried over Na2SO4, filtered and the filtrate was concentrated and purified by chromatography (silica, hexanes: acetone, 3:1) to give the title compound.

Workup

  1. temperaturethe reaction mixture was cooled to 0° C. and to it
  2. stirringThe reaction mixture was stirred at rt for 2 h
  3. washwashed with sat. NaHCO3 solution
  4. dry with materialThe organic fraction was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated
  7. custompurified by chromatography (silica, hexanes: acetone, 3:1)

Sources & evidence

ORD record
ord-69f7d23be2bf48e2ae6a24deb9ec1241
Source dataset
uspto-grants-2001_10
Patent number
US06303593B1

Reaction notes

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