1,2-Difluorobenzene → HCID 12801622, compound

HRID 1660354Notes

Reaction equation

HRID 1660354 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][CH2:9][C:10]3([CH2:15][CH2:14][N:13]([CH3:16])[CH2:12][CH2:11]3)[C:5]2=[CH:4][CH:3]=1.[H-].[Na+].[CH:19]1[CH:24]=[C:23]([F:25])[C:22](F)=[CH:21][CH:20]=1.[C:27]([OH:34])(=[O:33])/[CH:28]=[CH:29]\[C:30]([OH:32])=[O:31]>CCOCC.CS(C)=O>[C:27]([OH:34])(=[O:33])/[CH:28]=[CH:29]\[C:30]([OH:32])=[O:31].[Cl:1][C:2]1[CH:7]=[C:6]2[N:8]([C:22]3[CH:21]=[CH:20][CH:19]=[CH:24][C:23]=3[F:25])[CH2:9][C:10]3([CH2:15][CH2:14][N:13]([CH3:16])[CH2:12][CH2:11]3)[C:5]2=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 97061,2-DifluorobenzeneHCID 24758Sodium hydrideHCID 444266Maleic AcidHCID 128016176-Chloro-1'-methylspiro[indoline-3,4'-piperidine]

Product 1

HCID 12801622HCID 12801622, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 6.3 g of 6-chloro-1'-methylspiro[indoline-3,4'-piperidine], Example 23b, 1.5 g of sodium hydride, 10 g of O-difluorobenzene and 50 ml of dimethylsulfoxide is stirred at 60° C. under nitrogen for 30 minutes. Thereafter, the mixture is permitted to cool before adding ice-water. The biphasic mixture is extracted thrice with ether. The combined ether extracts are extracted with a large excess of dilute hydrochloric acid. The acidic extract is basified with concentrated ammonium hydroxide effecting a heavy oil. The oil is purified by passing through an alumina column, ether eluant, to provide a yellowish oil. The oil, in ether, is converted to its maleic acid salt which is recrystallized from an acetone-ether mixture providing off-white crystals, mp 166°-168° C. of 6-chloro-1-(2-fluorophenyl)-1'-methylspiro[indoline-3,4'-piperidine] maleate.

Workup

  1. temperatureto cool
  2. extractionThe biphasic mixture is extracted thrice with ether
  3. extractionThe combined ether extracts are extracted with a large excess of dilute hydrochloric acid
  4. extractionThe acidic extract
  5. customThe oil is purified
  6. customto provide a yellowish oil
  7. customis recrystallized from an acetone-ether mixture

Sources & evidence

ORD record
ord-b61706c35201421497dce93cf74339c0
Source dataset
uspto-grants-1981_12
Patent number
US04307235

Reaction notes

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