tert-Butyl 4-oxopiperidine-1-carboxylate → 4-((R)-7-methoxy-1,2,3,4-tetrahydro-naphthalen-2-ylamino)-piperidine-1-carboxylic acid tert-butyl ester

HRID 393209Notes

Reaction equation

HRID 393209 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:13]=[C:12]2[C:7]([CH2:8][CH2:9][C@@H:10]([NH2:14])[CH2:11]2)=[CH:6][CH:5]=1.[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][C:25](=O)[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C>[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH:25]([NH:14][C@@H:10]2[CH2:9][CH2:8][C:7]3[C:12](=[CH:13][C:4]([O:3][CH3:2])=[CH:5][CH:6]=3)[CH2:11]2)[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]

Participants

5

Reactant 3

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 44784815(R)-7-Methoxy-1,2,3,4-tetrahydro-naphthalen-2-ylamine hydrochloride

Product 1

HCID 693573464-((R)-7-methoxy-1,2,3,4-tetrahydro-naphthalen-2-ylamino)-piperidine-1-carboxylic acid tert-butyl esterYield 95.8%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of (R)-7-methoxy-1,2,3,4-tetrahydro-naphthalen-2-ylamine hydrochloride (6.0g, 28.1 mmol)(prepared as described in the French patent FR 2,653,765 or available commercially) and 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (6.7g, 33.7 mmol, 1.2 eq.) in dichloroethane (200 mL) under an inert atmosphere was added sodium triacetoxyborohydride (14.9 g, 70.2 mmol, 2.5 eq). The reaction was stirred at room temperature for 24 h then concentrated in vacuo. The residue was partitioned between EtOAc (200 mL) and 5% KOH (150 mL). The aqueous layer was extracted twice more with EtOAc (2×75 mL). The combined organic layers were dried (MgSO4), filtered, and concentrated to afford 4-((R)-7-methoxy-1,2,3,4-tetrahydro-naphthalen-2-ylamino)-piperidine-1-carboxylic acid tert-butyl ester as a yellow oil (9.7 g).

Workup

  1. concentrationthen concentrated in vacuo
  2. customThe residue was partitioned between EtOAc (200 mL) and 5% KOH (150 mL)
  3. extractionThe aqueous layer was extracted twice more with EtOAc (2×75 mL)
  4. dry with materialThe combined organic layers were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-9583318ae92f447684d1074c260910d7
Source dataset
uspto-grants-2004_10
Patent number
US06806278B2

Reaction notes

Loading…