4-Nitrobenzoic Acid → (6S,9R)-6-(2,3-difluorophenyl)-6-hydroxy-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-yl 4-nitrobenzoate
Reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@:9]1([OH:21])[CH2:19][CH2:18][C@H:17]([OH:20])[C:12]2=[N:13][CH:14]=[CH:15][CH:16]=[C:11]2[CH2:10]1.[N+:22]([C:25]1[CH:33]=[CH:32][C:28]([C:29](O)=[O:30])=[CH:27][CH:26]=1)([O-:24])=[O:23].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[N+:22]([C:25]1[CH:26]=[CH:27][C:28]([C:29]([O:20][C@H:17]2[C:12]3=[N:13][CH:14]=[CH:15][CH:16]=[C:11]3[CH2:10][C@@:9]([C:3]3[CH:4]=[CH:5][CH:6]=[C:7]([F:8])[C:2]=3[F:1])([OH:21])[CH2:19][CH2:18]2)=[O:30])=[CH:32][CH:33]=1)([O-:24])=[O:23]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
In a 250 mL round-bottom flask was dissolved (6S,9S)-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine-6,9-diol (458 mg, 1.572 mmol) (azeotroped with dry benzene) in tetrahydrofuran (8 mL) to give a light orange solution. 4-Nitrobenzoic acid (394 mg, 2.358 mmol) and triphenylphosphine (619 mg, 2.358 mmol) were added under nitrogen. Diisopropyl azodicarboxylate (0.464 mL, 2.358 mmol) was added dropwise. The mixture was allowed to stir overnight. After 15 h, LCMS showed complete conversion, but the desired product was a minor component. It was concentrated to a light yellow oil and directly purified by FCC (5% ethyl acetate/hexanes to 100%) to afford the desired product (125 mg, 18%) as a white solid. MS(ESI)[M+H+]=441.20.
Workup
- customto give a light orange solution
- waitAfter 15 h
Sources & evidence
- ORD record
- ord-bf4f56cefd6c4951b37598efdd3f57b7
- Source dataset
- uspto-grants-2012_11
- Patent number
- US08314117B2
Reaction notes
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