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Thionyl Chloride → 3-(Azidomethyl)-8-chloro-2-(5-fluoro-2-methoxyphenyl)quinoline

HRID 1397736
Notes
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Reaction equation

HRID 1397736 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1[O:19][CH3:20])[C:8]([CH:21]=O)=[CH:7]2.[BH4-].[Na+].S(Cl)(Cl)=O.[N-:29]=[N+:30]=[N-:31].[Na+]>C1COCC1.O.C(Cl)(Cl)Cl>[N:29]([CH2:21][C:8]1[C:9]([C:12]2[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=2[O:19][CH3:20])=[N:10][C:11]2[C:6]([CH:7]=1)=[CH:5][CH:4]=[CH:3][C:2]=2[Cl:1])=[N+:30]=[N-:31]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 24386Thionyl ChlorideHCID 33557Sodium AzideHCID 4311764Sodium borohydrideHCID 577079228-Chloro-2-(5-fluoro-2-methoxyphenyl)quinoline-3-carbaldehyde

Product 1

HCID 577079883-(Azidomethyl)-8-chloro-2-(5-fluoro-2-methoxyphenyl)quinoline

Reagents, catalysts & solvents 3

HCID 962
Water
Solvent
2×
HCID 6212ChloroformSolvent
HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 8-chloro-2-(5-fluoro-2-methoxyphenyl)quinoline-3-carb-aldehyde (385.4 mg, 1.221 mmol) in THF (6.0 mL) was added sodium borohydride (1.831 mmol) at rt. The solution was stirred 1 hour then diluted with water, and extracted with EtOAc to provide a crude solid after solvent removal, which was used without further purification. To the crude alcohol in CHCl3 (6 mL) was added thionyl chloride (0.445 mL, 6.103 mmol) at r.t. and stirred overnight. After 14 h the solvents were removed (TLC indicates complete.) The solid was dissolved in DMF (6 mL) then sodium azide (2.441 mmol) was added at once, and stirred 1 hour, poured into water and extracted EtOAc to give a crude material: 373.3 mg Chromatography, gradient 89/9/1.

Workup

  1. extractionextracted with EtOAc
  2. customto provide a crude solid
  3. customafter solvent removal, which
  4. customwas used without further purification
  5. stirringstirred overnight
  6. customAfter 14 h the solvents were removed (TLC indicates complete.) The solid
  7. dissolutionwas dissolved in DMF (6 mL)
  8. stirringstirred 1 hour
  9. extractionextracted EtOAc

Sources & evidence

ORD record
ord-cb8aa3160443427cb60b90419ba22bf7
Source dataset
uspto-grants-2014_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08901135B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes