Propanal → ((r)-7-Methoxy-1,2,3,4-tetrahydro-naphthalen-2-yl)-piperidin-4-yl-propyl-amine
Reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C@@H:15]2[CH2:24][CH2:23][C:22]3[C:17](=[CH:18][C:19]([O:25][CH3:26])=[CH:20][CH:21]=3)[CH2:16]2)[CH2:10][CH2:9]1)=O)(C)(C)C.[CH:27](=O)[CH2:28][CH3:29].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C>[CH3:26][O:25][C:19]1[CH:18]=[C:17]2[C:22]([CH2:23][CH2:24][C@@H:15]([N:14]([CH:11]3[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]3)[CH2:27][CH2:28][CH3:29])[CH2:16]2)=[CH:21][CH:20]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of 4-((R)-7-methoxy-1,2,3,4-tetrahydro-naphthalen-2-ylamino)-piperidine-1-carboxylic acid tert-butyl ester (9.7 g, 23.4 mmol) and propionaldehyde (2.0 mL, 28.1 mmol) in dichloroethane (150 mL) under a nitrogen atmosphere was added sodium triacetoxyborohydride (10.9 mg, 51.5 mmol) in a single portion. The reaction was stirred at room temperature for 24 h then concentrated in-vacuo. The residue was partitioned between EtOAc (175 mL) and 5% aq. KOH (150 mL). The aqueous phase was extracted twice more with EtOAc (2×30 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated to afford 10.0 g of the protected amine, which was treated with trifluoroacetic acid as described herein to afford ((R)-7-methoxy-1,2,3,4-tetrahydro-naphthalen-2-yl)-piperidin-4yl-propyl-amine (7.0 g).
Workup
- concentrationthen concentrated in-vacuo
- customThe residue was partitioned between EtOAc (175 mL) and 5% aq. KOH (150 mL)
- extractionThe aqueous phase was extracted twice more with EtOAc (2×30 mL)
- dry with materialThe combined organic layers were dried over MgSO4
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-6ac699ae1582434083ceaad3a27159d7
- Source dataset
- uspto-grants-2004_10
- Patent number
- US06806278B2
Reaction notes
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