Acetaldehyde → 4-{[Ethyl-(7-nitro-1,2,3,4-tetrahydro-naphthalen-2-yl)-amino]-methyl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 983455Notes

Reaction equation

HRID 983455 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][NH:15][CH:16]2[CH2:25][CH2:24][C:23]3[C:18](=[CH:19][C:20]([N+:26]([O-:28])=[O:27])=[CH:21][CH:22]=3)[CH2:17]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:29](=O)[CH3:30].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][N:15]([CH2:29][CH3:30])[CH:16]2[CH2:25][CH2:24][C:23]3[C:18](=[CH:19][C:20]([N+:26]([O-:28])=[O:27])=[CH:21][CH:22]=3)[CH2:17]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 177AcetaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 112922004-[(7-Nitro-1,2,3,4-tetrahydro-naphthalen-2-ylamino)-methyl]-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 686240424-{[Ethyl-(7-nitro-1,2,3,4-tetrahydro-naphthalen-2-yl)-amino]-methyl)-piperidine-1-carboxylic acid tert-butyl esterYield 82.4%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of 4-[(7-nitro-1,2,3,4-tetrahydro-naphthalen-2-ylamino)-methyl]-piperidine-1-carboxylic acid tert-butyl ester (485 mg, 1.25 mmol) and acetaldehyde (110 μL, 1.49 mmol) in dichloroethane (20 mL) under a nitrogen atmosphere was added sodium triacetoxyborohydride (530 mg, 2.49 mmol, 2 eq.) in a single portion. The reaction was stirred at room temperature for 24 h then concentrated in vacuo. The residue was partitioned between EtOAc (75 mL) and 5% aq. KOH (50 mL). The aqueous phase was extracted twice more with EtOAc (2×30 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated onto silica (10 g). This was placed on top of a flash column and eluted with 20% acetone in hexanes. The fractions containing product were pooled and concentrated to afford 4-{[ethyl-(7-nitro-1,2,3,4-tetrahydro-naphthalen-2-yl)-amino]-methyl}-piperidine-1-carboxylic acid tert-butyl ester as a yellow oil (430 mg).

Workup

  1. concentrationthen concentrated in vacuo
  2. customThe residue was partitioned between EtOAc (75 mL) and 5% aq. KOH (50 mL)
  3. extractionThe aqueous phase was extracted twice more with EtOAc (2×30 mL)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated onto silica (10 g)
  7. washeluted with 20% acetone in hexanes
  8. additionThe fractions containing product
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-3ba9b6d6b9394331ab2f9411429a6e27
Source dataset
uspto-grants-2005_03
Patent number
US06864266B2

Reaction notes

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