Triphenylphosphine → 4-Chloro-6-cyano-7-(3-(pyrrolidin-1-yl)propoxy)quinoline

HRID 2222401Notes

Reaction equation

HRID 2222401 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([OH:14])=[C:9]([C:12]#[N:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.[N:15]1([CH2:20][CH2:21][CH2:22]O)[CH2:19][CH2:18][CH2:17][CH2:16]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C(Cl)Cl>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:22][CH2:21][CH2:20][N:15]3[CH2:19][CH2:18][CH2:17][CH2:16]3)=[C:9]([C:12]#[N:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 2093421-PyrrolidinepropanolHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 1355837304-Chloro-6-cyano-7-hydroxyquinoline

Product 1

HCID 597122344-Chloro-6-cyano-7-(3-(pyrrolidin-1-yl)propoxy)quinolineYield 90.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 4-chloro-6-cyano-7-hydroxyquinoline (10.22 g, 50 mmol), (prepared as described for the starting material in Example 1), 3-(pyrrolidin-1-yl)propan-1-ol (8.1 ml, 60 mmol) and triphenylphosphine (26.2 g, 100 mmol) in methylene chloride (200 ml) was added diethyl azodicarboxylate (16.4 ml, 100 mmol) in portions. After stirring the reaction mixture for 2 hours at ambient temperature, the volatiles were removed under vacuum and the residue was purified by column chromatography eluting with ethyl acetate/methylene chloride (1/1) followed by methanol/ethyl acetate/methylene choride (1/4/5 followed by 1/0/9) followed by methanol saturated with ammonia/methylene chloride (1/9 followed by 2/8). The fractions containing the expected product were combined and the volatiles were removed under vacuum. The residue was triturated with ether, collected by filtration, washed with ether and dried under vacuum to give 4-chloro-6-cyano-7-(3-(pyrrolidin-1-yl)propoxy)quinoline (14.3 g, 90%).

Workup

  1. custom(prepared
  2. customthe volatiles were removed under vacuum
  3. customthe residue was purified by column chromatography
  4. washeluting with ethyl acetate/methylene chloride (1/1)
  5. additionThe fractions containing the expected product
  6. customthe volatiles were removed under vacuum
  7. customThe residue was triturated with ether
  8. filtrationcollected by filtration
  9. washwashed with ether
  10. customdried under vacuum

Sources & evidence

ORD record
ord-76199c1ae8bf4f9aa99b4af30d574826
Source dataset
uspto-grants-2008_05
Patent number
US07371765B2

Reaction notes

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