N,N,N',N'-Tetramethylethylenediamine → 1-Tert-butyl 4-methyl 4-(2-((tert-butoxycarbonyl)amino)-1-hydroxyethyl)piperidine-1,4-dicarboxylate

HRID 1501796Notes

Reaction equation

HRID 1501796 reaction equation
[Li+].CC([N-]C(C)C)C.[N:9]1([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14][CH2:13][CH:12]([C:15]([O:17][CH3:18])=[O:16])[CH2:11][CH2:10]1.CN(CCN(C)C)C.[O:34]=[CH:35][CH2:36][NH:37][C:38](=[O:44])[O:39][C:40]([CH3:43])([CH3:42])[CH3:41]>C1COCC1>[C:40]([O:39][C:38]([NH:37][CH2:36][CH:35]([C:12]1([C:15]([O:17][CH3:18])=[O:16])[CH2:11][CH2:10][N:9]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14][CH2:13]1)[OH:34])=[O:44])([CH3:43])([CH3:42])[CH3:41]

Participants

6

Reactant 4

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 3928701-N-Boc-4-Piperidinecarboxylic acid methyl esterHCID 2724682Lithium diisopropylamideHCID 4247255tert-butyl N-(2-oxoethyl)carbamate

Product 1

HCID 867094901-Tert-butyl 4-methyl 4-(2-((tert-butoxycarbonyl)amino)-1-hydroxyethyl)piperidine-1,4-dicarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of LDA (prepared by adding n-butyllithium (20.0 mL, 49.3 mmol) to diisopropylamine (5.16 mg, 51.0 mmol) in THF (40 mL) at 0° C., stirred for 30 min) was added 1-tert-butyl 4-methyl piperidine-1,4-dicarboxylate (4.00 g, 16.4 mmol) in TMEDA (15 mL, 99 mmol) drop-wise via syringe pump at −78° C. for 10 min. The mixture was stirred at the same temperature for 30 min, then tert-butyl (2-oxoethyl)carbamate (8.11 g, 51.0 mmol) in THF (20 mL) was added slowly by syringe pump for 15 min. The mixture was stirred at −78° C. for 30 min, quenched with saturated NH4Cl at −78° C., warmed up to rt and diluted with EtOAc (200 mL). The organic layer was separated, and the aqueous layer was extracted with EtOAc (100 mL). The combined organic layers were washed with brine, dried (MgSO4), and concentrated. The residue was purified by column chromatography (80 g, silical gel, MeOH/DCM, gradient 0-10%, monitor at 210 nm) to afford title compound. LC/MS: [(M+1)]+=403

Workup

  1. stirringThe mixture was stirred at −78° C. for 30 min
  2. customquenched with saturated NH4Cl at −78° C.
  3. additiondiluted with EtOAc (200 mL)
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with EtOAc (100 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography (80 g, silical gel, MeOH/DCM, gradient 0-10%, monitor at 210 nm)

Sources & evidence

ORD record
ord-3fbd7a21e8534beb9fe3f9b610a27b93
Source dataset
uspto-grants-2015_12
Patent number
US09206198B2

Reaction notes

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