Triethylamine → Pitavastatin Ethyl Ester

HRID 1072292Notes

Reaction equation

[CH2:1]([O:3][C:4](=[O:33])[CH2:5][C:6](=[O:32])[CH2:7][C:8](=[O:31])/[CH:9]=[CH:10]/[C:11]1[C:12]([CH:28]2[CH2:30][CH2:29]2)=[N:13][C:14]2[C:19]([C:20]=1[C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=1)=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH3:2].C(N(CC)CC)C.C(O)=O.C(N(CC)CC)C>CN(C)C=O>[CH2:1]([O:3][C:4](=[O:33])[CH2:5][C@H:6]([OH:32])[CH2:7][C@H:8]([OH:31])/[CH:9]=[CH:10]/[C:11]1[C:12]([CH:28]2[CH2:29][CH2:30]2)=[N:13][C:14]2[C:19]([C:20]=1[C:21]1[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=1)=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH3:2]

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of (E)-7-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-3,5-dioxo-hept-6-enoic acid ethyl ester (600 mg, 1.347 mmol) in N,N-dimethylformamide (5 ml) under argon is added (1R,2R)-N-p-toluenesulfonyl-1,2-diphenylethylenediamine-RuII-pcymene complex [cf. above] (40 mg, 0.067 mmol) and formic acid-triethylamine 5:2 (v/v)-mixture (2 ml). After stirring at 50° C. for 30 min, triethylamine (4.7 ml, 33.79 mmol) is added to the orange, clear solution, and stirring is continued at 50° C. for 19 hours. Evaporation of the reaction mixture under reduced pressure, followed by silica gel chromatography (toluene/ethyl acetate 3:1) of the dried residue affords (E)-(3R,5S)-7-[2-Cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-3,5-dihydroxy-hept-6-enoic acid ethyl ester. MS (EI): [M+]447, diastereomeric purity (syn/anti): 90.0/10.0%, enantiomeric purity (3R5S/3S5R): 80.0/20.0% (HPLC on ChiralPak AD-column).

Workup

stirringstirring
waitis continued at 50° C. for 19 hours
customEvaporation of the reaction mixture under reduced pressure

Sources & evidence

ORD record: ord-7522ecb75b414506864d0e4cd465d7b0
Source dataset: uspto-grants-2005_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06909003B2

Reaction notes

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