[8-(Benzyloxy)-5-chloroquinolin-7-yl]acetaldehyde → 2-(8-Benzyloxy-5-chloro-quinolin-7-yl)-1-(3-pyrrolidin-1-ylmethyl-phenyl)-ethanol

HRID 551125Notes

Reaction equation

HRID 551125 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([CH2:20][CH:21]=[O:22])=[CH:11][C:12]([Cl:19])=[C:13]2[C:18]=1[N:17]=[CH:16][CH:15]=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:23]1([CH2:28][C:29]2[CH:30]=[C:31]([Mg]Br)[CH:32]=[CH:33][CH:34]=2)[CH2:27][CH2:26][CH2:25][CH2:24]1>O1CCCC1>[CH2:1]([O:8][C:9]1[C:10]([CH2:20][CH:21]([C:31]2[CH:32]=[CH:33][CH:34]=[C:29]([CH2:28][N:23]3[CH2:24][CH2:25][CH2:26][CH2:27]3)[CH:30]=2)[OH:22])=[CH:11][C:12]([Cl:19])=[C:13]2[C:18]=1[N:17]=[CH:16][CH:15]=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 59829696[8-(Benzyloxy)-5-chloroquinolin-7-yl]acetaldehydeHCID 178419627HCID 178419627, compound

Product 1

HCID 671720482-(8-Benzyloxy-5-chloro-quinolin-7-yl)-1-(3-pyrrolidin-1-ylmethyl-phenyl)-ethanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a stirring solution of [8-(benzyloxy)-5-chloroquinolin-7-yl]acetaldehyde (10.54 mmol) in tetrahydrofuran (75 mL) at −78° C. was slowly added a 0.25M solution of [3-(1-pyrrolidinylmethyl)phenyl]magnesium bromide in tetrahydrofuran (12.50 mmol, 1.2 eq.) and stirring at −78° C. was continued for 20 min. The reaction mixture was then quenched with saturated aqueous ammonium chloride solution (10 mL) and allowed to warm to room temperature. The mixture was then diluted with saturated aqueous ammonium chloride solution (65 mL) and extracted with ethyl acetate (2×75 mL). The combined organic layers were dried (MgSO4), filtered and concentrated to give 2-(8-benzyloxy-5-chloro-quinolin-7-yl)-1-(3-pyrrolidin-1-ylmethyl-phenyl)-ethanol as a yellow oil that was purified by column chromatography using 70/29/1 dichloromethane/acetone/diisopropylethylamine. The 2-(8-benzyloxy-5-chloro-quinolin-7-yl)-1-(3-pyrrolidin-1-ylmethyl-phenyl)-ethanol was subjected to the general conditions described above for conversion of alcohols to azides to give 7-[2-Azido-2-(3-pyrrolidin-1-ylmethyl-phenyl)-ethyl]-8-benzyloxy-5-chloro-quinoline. 7-[2-Azido-2-(3-pyrrolidin-1-ylmethyl-phenyl)-ethyl]-8-benzyloxy-5-chloro-quinoline (5.34 mmol) was subjected to the general conditions described above for Staudinger reduction of azides to give 2-(8-Benzyloxy-5-chloro-quinolin-7-yl)-1-(3-pyrrolidin-1-ylmethyl-phenyl)-ethylamine an amber oil and was used directly in the ensuing step. 2-(8-Benzyloxy-5-chloro-quinolin-7-yl)-1-(3-pyrrolidin-1-ylmethyl-phenyl)-ethylamine (0.675 mmol) was subjected to the general conditions described above for N-acylation with 4-biphenylcarbonyl chloride to give an off-white solid which was purified by twice recrystallizing from dichloromethane/hexanes to give the title compound as a white solid (0.311 mmol, 18% for 4 steps). MS (ESI) m/z 652.5; HRMS: calcd for C42H38ClN3O2+H+, 652.27253; found (ESI, [M+H]+ Obs'd), 652.2730.

Workup

  1. customThe reaction mixture was then quenched with saturated aqueous ammonium chloride solution (10 mL)
  2. temperatureto warm to room temperature
  3. additionThe mixture was then diluted with saturated aqueous ammonium chloride solution (65 mL)
  4. extractionextracted with ethyl acetate (2×75 mL)
  5. dry with materialThe combined organic layers were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-55f61b3fa420459fbe43a4a9e1ea261b
Source dataset
uspto-grants-2011_05
Patent number
US07947712B2

Reaction notes

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