Diisopropylamine → HCID 117603899, compound

HRID 1481964Notes

Reaction equation

HRID 1481964 reaction equation
C(NC(C)C)(C)C.[Li][CH2:9][CH2:10][CH2:11][CH3:12].[N:13]1([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:18][CH2:17][CH:16]([C:19]([O:21][CH3:22])=[O:20])[CH2:15][CH2:14]1.CN(P(N(C)C)(N(C)C)=O)C.BrCCC=C.[NH4+].[Cl-]>CCCCCC.C1COCC1>[CH2:9]([C:16]1([C:19]([O:21][CH3:22])=[O:20])[CH2:15][CH2:14][N:13]([C:23]([O:25][C:26]([CH3:27])([CH3:28])[CH3:29])=[O:24])[CH2:18][CH2:17]1)[CH2:10][CH:11]=[CH2:12]

Participants

9

Reactant 6

HCID 7912DiisopropylamineHCID 12679HexamethylphosphoramideHCID 21241Homoallyl bromideHCID 25517Ammonium ChlorideHCID 3928701-N-Boc-4-Piperidinecarboxylic acid methyl esterHCID 178418339Butyllithium

Product 1

HCID 117603899HCID 117603899, compoundYield 72%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

A mixture of diisopropylamine (17.57 mL, 123 mmol) and THF (300 mL) was cooled to −78° C. and 1.6 M solution of n-BuLi (77 mL, 123 mmol) in hexane was added slowly. The mixture was stirred for 15 min, warmed to 0° C. for 20 min and cooled back to −78° C. 1-tert-Butyl 4-methyl piperidine-1,4-dicarboxylate (25 g, 103 mmol) in THF (25 mL) was added dropwise and the mixture was stirred for 40 min. Then, a mixture of HMPA (17.88 mL, 103 mmol) and 4-bromobut-1-ene (27.7 g, 206 mmol) was added and the mixture was stirred for 1 h before it was warmed to room temp and stir for 16 h. Sat. NH4Cl was then added and the mixture was extracted with ether (2×500 mL), dried (Na2SO4), filtered and concentrated. The residue was purified by Biotage (0-20% EtOAc/hexane; 300 g column) to afford 1-tert-butyl 4-methyl 4-(but-3-en-1-yl)piperidine-1,4-dicarboxylate (22 g, 74.0 mmol, 72.0% yield) as light yellow oil. 1H NMR (500 MHz, CDCl3) δ 5.76 (ddt, J=17.0, 10.3, 6.5 Hz, 1H), 5.06-4.92 (m, 2H), 3.94-3.85 (m, 2H), 3.73 (s, 3H), 2.95-2.80 (m, 2H), 2.13 (d, J=13.1 Hz, 2H), 2.02-1.93 (m, 2H), 1.64-1.58 (m, 2H), 1.47 (s, 9H), 1.42-1.32 (m, 2H). LCMS (M+H)=298.2.

Workup

  1. temperaturewarmed to 0° C. for 20 min
  2. temperaturecooled back to −78° C
  3. stirringthe mixture was stirred for 40 min
  4. additionwas added
  5. stirringthe mixture was stirred for 1 h before it
  6. temperaturewas warmed to room temp
  7. stirringstir for 16 h
  8. extractionthe mixture was extracted with ether (2×500 mL)
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was purified by Biotage (0-20% EtOAc/hexane; 300 g column)

Sources & evidence

ORD record
ord-f18aa923b11740208d80822a4104f17a
Source dataset
uspto-grants-2016_08
Patent number
US09409922B2

Reaction notes

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