Tetrahydrofuran → HCID 13324737, compound

HRID 371499Notes

Reaction equation

HRID 371499 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]#[N:19])[CH:13]=1)[CH2:6][CH2:5]2.C1COCC1.[H-].[H-].[H-].[H-].[Li+].[Al+3].[C:31]([OH:38])(=[O:37])/[CH:32]=[CH:33]/[C:34]([OH:36])=[O:35]>C(O)C>[C:31]([OH:38])(=[O:37])/[CH:32]=[CH:33]/[C:34]([OH:36])=[O:35].[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]1[CH:13]=[C:14]([CH2:18][NH2:19])[CH:15]=[CH:16][CH:17]=1)[CH2:6][CH2:5]2

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 444972Fumaric AcidHCID 13324713HCID 13324713, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 13324737HCID 13324737, compoundYield 84.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

A solution of 4.41 g (16.4 mmole) of α-(5-chloro-1-indolinyl)-m-tolunitrile of Example 17a in 30 ml distilled THF was added dropwise over 30 minutes to a rapidly stirred ice cold slurry of 2.49 g (65.6 mmole, 4.0 equivalents) LiAlH4 in 65 ml distilled THF under nitrogen. After warming to room temperature, the mixture was heated under reflux for 2.75 hours, cooled in an ice bath, and quenched by dropwise addition of 2.5 ml water, 2.5 ml 10% NaOH, and 7.5 ml water. The salts were filtered and washed with 250 ml boiling methylene chloride. The filtrate was concentrated and the residue was dissolved in methylene chloride (100 ml), washed with brine (250 ml), dried over K2CO3, and concentrated to give 4.29 g (95.9%) of crude free base. The free base (4.23 g, 15.5 mmole) was dissolved in 30 ml absolute ethanol and added to a warm solution of 1.80 g (15.5 mmole) fumaric acid in 80 ml absolute ethanol. The fumarate salt slowly crystallized upon cooling to room temperature, thus affording 5.12 g (84.9%) of 3-(5-chloro-1-indolinylmethyl)benzenemethanamine fumarate, m.p. 178° C., dec.

Workup

  1. distillationdistilled THF under nitrogen
  2. temperaturethe mixture was heated
  3. temperatureunder reflux for 2.75 hours
  4. temperaturecooled in an ice bath
  5. customquenched by dropwise addition of 2.5 ml water, 2.5 ml 10% NaOH, and 7.5 ml water
  6. filtrationThe salts were filtered
  7. washwashed with 250 ml
  8. concentrationThe filtrate was concentrated
  9. dissolutionthe residue was dissolved in methylene chloride (100 ml)
  10. washwashed with brine (250 ml)
  11. dry with materialdried over K2CO3
  12. concentrationconcentrated
  13. customto give 4.29 g (95.9%) of crude free base
  14. customThe fumarate salt slowly crystallized
  15. temperatureupon cooling to room temperature

Sources & evidence

ORD record
ord-4c4aff60fce3407e9aafe2335e7fc6b5
Source dataset
uspto-grants-1985_07
Patent number
US04532333

Reaction notes

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