Diisopropylamine → HCID 67051702, compound

HRID 1809030Notes

Reaction equation

HRID 1809030 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.CCCCCC.[CH3:19][CH:20]1[N:25]([CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:24]([C:33]#[N:34])[CH2:23][CH2:22][CH2:21]1.[O:35]=[C:36]1[CH2:39][N:38]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:37]1>C1COCC1>[C:33]([C:24]1([C:36]2([OH:35])[CH2:37][N:38]([C:40]([O:42][C:43]([CH3:45])([CH3:44])[CH3:46])=[O:41])[CH2:39]2)[CH2:23][CH2:22][CH2:21][CH:20]([CH3:19])[N:25]1[CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)#[N:34]

Participants

7

Reactant 5

HCID 7912DiisopropylamineHCID 8058HexaneHCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterHCID 67051796HCID 67051796, compoundHCID 178418339Butyllithium

Product 1

HCID 67051702HCID 67051702, compoundYield 7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of N,N-diisopropylamine (1.6 mL, 11.2 mmol) cooled to −78° C. in THF (15 mL) was added a 2.5 M solution of n-BuLi in hexane (4.5 mL, 11.2 mmol) dropwise over 5 minutes and the mixture was stirred at this temperature for an addition 15 minutes. 6-methyl-1-(phenylmethyl)piperidine-2-carbonitrile (2.4 g, 11.2 mmol) (prepared using procedures similar to those in Bonin et. al. Tet. Lett. 1982, 23(33), 3369-72) in THF (10 mL) was then added dropwise over 20 minutes and the reaction mixture was stirred for a further minutes. Next a solution of 1,1-dimethylethyl 3-oxoazetidine-1-carboxylate (1.3 g, 7.5 mmoL), prepared using procedures similar to those in Example 3, in THF (10 mL) was added dropwise over 30 minutes. The reaction mixture was gradually warmed to room temperature and allowed to stir overnight. The reaction mixture was quenched with 10% citric acid and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with water, brine, dried over anhydrous sodium sulfate then filtered and concentrated in vacuo to give crude product as yellow oil. Further purification by flash chromatography (30% ethyl acetate in hexanes) afforded 1,1-dimethylethyl 3-[2-cyano-6-methyl-1-(phenylmethyl)piperidin-2-yl]-3-hydroxyazetidine-1-carboxylate as a pale yellow oil (0.2 g, 7% yield). 1H NMR (400 MHz, CDCl3): 7.17-7.40 (m, 5H), 4.42 (d, 1H), 4.04-4.18 (m, 1H), 3.83-4.00 (m, 1H), 3.70-3.75 (m, 2H), 1.70-1.87 (m, 4H), 1.45 (s, 3H), 1.41 (s, 9H), 1.22-1.26 (m, 1H), 1.13-1.18 (m, 2H); MS (EI) for C22H31N3O3: 386 (MH+).

Workup

  1. stirringthe reaction mixture was stirred for a further minutes
  2. stirringto stir overnight
  3. customThe reaction mixture was quenched with 10% citric acid
  4. extractionextracted with ethyl acetate (3×50 mL)
  5. washThe combined organic layers were washed with water, brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationthen filtered
  8. concentrationconcentrated in vacuo
  9. customto give crude product as yellow oil
  10. customFurther purification by flash chromatography (30% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-37a8f8838eac408eb1df9bf7b97a6631
Source dataset
uspto-grants-2013_01
Patent number
US08362002B2

Reaction notes

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