Norcamphor → 1'-(Bicyclo[2.2.1]heptan-2-yl)spiro[indene-1,4'-piperidine]-3-carboxylic acid
Reaction equation
[NH:1]1[CH2:6][CH2:5][C:4]2([C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[C:8]([C:15]([O-:17])=[O:16])=[CH:7]2)[CH2:3][CH2:2]1.[C@H:18]12[CH2:24][C@H:21]([CH2:22][CH2:23]1)[CH2:20][C:19]2=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH:18]12[CH2:24][CH:21]([CH2:22][CH2:23]1)[CH2:20][CH:19]2[N:1]1[CH2:6][CH2:5][C:4]2([C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[C:8]([C:15]([OH:17])=[O:16])=[CH:7]2)[CH2:3][CH2:2]1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Procedure
A mixture of compound (D1) (0.020 g, 0.058 mmol), titanium (IV) isopropoxide (0.052 mL, 0.174 mmol), and (1R,4S)-bicyclo[2.2.1]heptan-2-one (3 eq) was stirred at room temperature for 18 h in dichloroethane (0.5 mL). Sodium triacetoxyborohydride (0.012 g, 0.058 mmol) was added and stirred at room temperature for 1 h. The solvent was evaporated and 6N NaOH (0.5 mL) and methanol (1 mL) was added and then triturated to form a white solid. The solid was washed with methanol (1 mL) and EtOAc (1 mL). The filtrate was concentrated under reduced pressure to afford the crude product which was purified by reverse phase preparative HPLC to afford 1′-(bicyclo[2.2.1]heptan-2-yl)spiro[indene-1,4′-piperidine]-3-carboxylic acid (Compound No. 48) (0.002 g). LC/MS (10-90% over 3 min with 0.9% FA) m/z 324.1 (M+1), Rt 1.9 minutes.
Workup
- customThe solvent was evaporated
- addition6N NaOH (0.5 mL) and methanol (1 mL) was added
- customtriturated
- customto form a white solid
- washThe solid was washed with methanol (1 mL) and EtOAc (1 mL)
- concentrationThe filtrate was concentrated under reduced pressure
- customto afford the crude product which
- customwas purified by reverse phase preparative HPLC
Sources & evidence
- ORD record
- ord-521afdb25ee04734aff26c9130333caf
- Source dataset
- uspto-grants-2010_12
- Patent number
- US07858790B2
Reaction notes
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