Sodium Iodide → tert-Butyl [(3S,5S,6R)-6-methyl-1-(2-methylprop-2-en-1-yl)-2-oxo-5-phenylpiperidin-3-yl]carbamate

HRID 406551Notes

Reaction equation

HRID 406551 reaction equation
[CH3:1][C@H:2]1[NH:7][C:6](=[O:8])[C@@H:5]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:4][C@H:3]1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:34][C:35]([CH3:37])=[CH2:36].[I-].[Na+]>O1CCCC1.CN1CCCC1=O.O>[CH3:1][C@H:2]1[N:7]([CH2:36][C:35]([CH3:37])=[CH2:34])[C:6](=[O:8])[C@@H:5]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:4][C@H:3]1[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 3577853-Bromo-2-methyl-1-propeneHCID 2733832Lithium HexamethyldisilazideHCID 69096668tert-butyl N-((3S,5S,6R)-6-methyl-2-oxo-5-phenylpiperidin-3-yl)carbamate2×

Product 1

HCID 86665201tert-Butyl [(3S,5S,6R)-6-methyl-1-(2-methylprop-2-en-1-yl)-2-oxo-5-phenylpiperidin-3-yl]carbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 22156051tetrahydrofuran N-methylpyrrolidinoneSolvent

Conditions

Temperature
0 °C

Procedure

To a pre-cooled 0° C. solution of tert-butyl [(3S,5S,6R)-6-methyl-2-oxo-5-phenylpiperidin-3-yl]carbamate (described in Intermediate 9, step C, 0.20 g, 0.657 mmol) in tetrahydrofuran:N-methyl-2-pyrrolidinone (2:1, 4.0 mL) was added lithium bis(trimethylsilyl)amide (0.735 mL, 0.735 mmol, 1 M in THF) and the mixture was stirred at 0° C. for 10 min. 3-Bromo-2-methylpropene (0.31 mL, 3.29 mmol) and sodium iodide (0.098 g, 0.66 mmol) were added and the resulting mixture was stirred at 0° C. for 2 h and then warmed to 23° C. and stirred for an additional 18 h. The mixture was diluted with water and extracted with ethyl acetate (3×). The combined organic extracts were washed with water, brine, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography (20% ethyl acetate→80% ethyl acetate/hexane) afforded the title compound. MS: m/z=381.3 (M+Na).

Workup

  1. stirringthe resulting mixture was stirred at 0° C. for 2 h
  2. temperaturewarmed to 23° C.
  3. stirringstirred for an additional 18 h
  4. extractionextracted with ethyl acetate (3×)
  5. washThe combined organic extracts were washed with water, brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by silica gel chromatography (20% ethyl acetate→80% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-5dad26a69c7b445bbd35327a3960885a
Source dataset
uspto-grants-2014_06
Patent number
US08754096B2

Reaction notes

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