(3S)-pyrrolidin-3-ol → (S)-4-[4-(3-hydroxy-pyrrolidin-1-yl)-2-methyl-quinolin-7-yloxymethyl]-benzonitrile
Reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:12][CH2:13][C:14]3[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=3)=[CH:9][CH:10]=2)[N:5]=[C:4]([CH3:22])[CH:3]=1.[OH:23][C@H:24]1[CH2:28][CH2:27][NH:26][CH2:25]1>>[OH:23][C@H:24]1[CH2:28][CH2:27][N:26]([C:2]2[C:11]3[C:6](=[CH:7][C:8]([O:12][CH2:13][C:14]4[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=4)=[CH:9][CH:10]=3)[N:5]=[C:4]([CH3:22])[CH:3]=2)[CH2:25]1Participants
Procedure
A solution of 1.42 g of (4.6 mmol) of 4-(4-chloro-2-methyl-quinolin-7-yloxymethyl)-benzonitrile and 1.11 g (12.5 mmol) of (S)-3-hydroxypyrrolidine in 1-methyl-2-pyrrolidine (25 ml) was heated under nitrogen at 100° C. (oil bath temperature) for 23 h. The reaction mixture was concentrated in a high vacuum, the residue taken up in methylene chloride, which was washed with water, saturated NaCl solution and then dried over magnesium sulphate. The solvent was removed in vacuo, the residue triturated with MeOH, filtered off by suction, washed subsequently with MeOH and ether and then dried in a high vaccum to give 1.45 g (83.86%) of the (S)-4-[4-(3-hydroxy-pyrrolidin-1-yl)-2-methyl-quinolin-7-yloxymethyl]-benzonitrile as a brown solid. ISP mass spectrum, m/e: 360.2 (M+1 calculated for C22H21N3O2: 360.2).
Workup
- concentrationThe reaction mixture was concentrated in a high vacuum
- washwhich was washed with water, saturated NaCl solution
- dry with materialdried over magnesium sulphate
- customThe solvent was removed in vacuo
- customthe residue triturated with MeOH
- filtrationfiltered off by suction
- washwashed subsequently with MeOH and ether
- customdried in a high vaccum
Sources & evidence
- ORD record
- ord-491498adb21a4df6ad5b9f86b9b0001b
- Source dataset
- uspto-grants-2004_11
- Patent number
- US06818767B2
Reaction notes
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