4-(3-Chloro-4-methoxy-benzylamino)-6-cyano-8-ethyl-quinoline-3-carboxylic acid ethyl ester → 4-(3-Chloro-4-methoxy-benzylamino)-8-ethyl-3-hydroxymethyl-quinoline-6-carbonitrile

HRID 2224579Notes

Reaction equation

HRID 2224579 reaction equation
C([O:3][C:4]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[NH:16][CH2:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([Cl:26])[CH:19]=1)=[CH:13][C:12]([C:27]#[N:28])=[CH:11][C:10]=2[CH2:29][CH3:30])=O)C.C(O[AlH-](OC(C)(C)C)OC(C)(C)C)(C)(C)C.[Li+].C1COCC1>C1COCC1>[Cl:26][C:20]1[CH:19]=[C:18]([CH2:17][NH:16][C:15]2[C:14]3[C:9](=[C:10]([CH2:29][CH3:30])[CH:11]=[C:12]([C:27]#[N:28])[CH:13]=3)[N:8]=[CH:7][C:6]=2[CH2:4][OH:3])[CH:23]=[CH:22][C:21]=1[O:24][CH3:25]

Participants

4

Reactant 2

HCID 442873184-(3-Chloro-4-methoxy-benzylamino)-6-cyano-8-ethyl-quinoline-3-carboxylic acid ethyl esterHCID 131723922lithium tri-t-butoxyaluminohydride THF

Product 1

HCID 104524634-(3-Chloro-4-methoxy-benzylamino)-8-ethyl-3-hydroxymethyl-quinoline-6-carbonitrileYield 84%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 100 mg (0.236 mmol) of 4-[[(3-chloro-4-methoxyphenyl)methyl]amino]-6-cyano-8-ethylquinoline-3-carboxylic acid ethyl ester in 2.8 mL anhydrous THF under nitrogen, was added 1.2 mL (5.0 eq) of 1M lithium tri-t-butoxyaluminohydride/THF. The resulting mixture was refluxed overnight with stirring. The reaction was quenched with 1 mL of MeOH and partitioned between 75 mL 1M NaOH and 100 mL CH2Cl2. The organic phase was washed with 1M NaOH (2×30 mL) and dried over MgSO4. Removal of the solvent under reduced pressure gave 75 mg (84% yield) of the title compound as a light yellow solid. The analytical sample was obtained by trituration in ether: mp: 188-189° C. LC: 3.15′; MH+: 382.

Workup

  1. temperatureThe resulting mixture was refluxed overnight
  2. customThe reaction was quenched with 1 mL of MeOH
  3. custompartitioned between 75 mL 1M NaOH and 100 mL CH2Cl2
  4. washThe organic phase was washed with 1M NaOH (2×30 mL)
  5. dry with materialdried over MgSO4
  6. customRemoval of the solvent under reduced pressure

Sources & evidence

ORD record
ord-e763b9dfcb6541e985b38c720e1586bc
Source dataset
uspto-grants-2008_05
Patent number
US07378430B2

Reaction notes

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