Silane, trimethyl(2-propyn-1-yloxy)- → (2S,3R)-1-tert-Butoxycarbonyl-3-(3-hydroxypropyn-1-yl)-2-phenylpiperidin-3-ol

HRID 1976042Notes

Reaction equation

HRID 1976042 reaction equation
C([Mg]Br)C.C[Si]([O:9][CH2:10][C:11]#[CH:12])(C)C.[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH2:23][C:22](=[O:26])[C@@H:21]1[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:19])([CH3:16])([CH3:15])[CH3:14].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1.O>[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH2:23][C@:22]([C:12]#[C:11][CH2:10][OH:9])([OH:26])[C@@H:21]1[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

7

Reactant 4

HCID 79696Silane, trimethyl(2-propyn-1-yloxy)-HCID 2724141Tetrabutylammonium FluorideHCID 10956740(2S)-1-tert-butoxycarbonyl-2-phenylpiperidin-3-oneHCID 178418443HCID 178418443, compound

Product 1

HCID 11301992(2S,3R)-1-tert-Butoxycarbonyl-3-(3-hydroxypropyn-1-yl)-2-phenylpiperidin-3-ol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a cooled (−5° C.) solution of ethylmagnesium bromide (1M in tetrahydrofuran, 130 ml, 130 mmol) in tetrahydrofuran was added O-trimethylsilylpropargyl alcohol slowly. The reaction was stirred at 0° C. for 20 minutes and then at room temperature for 2 hours, before cooling to −10° C. To this was then added a solution of (2S)-1-tert-butyloxycarbonyl-2-phenylpiperidin-3-one (Desc. 1; 30 g, 108 mmol) in tetrahydrofuran keeping the temperature below 5° C. The reaction was stirred at room temperature overnight, quenched by addition of water/saturated aqueous ammonium chloride (200 ml/200 ml) and extracted with ethyl acetate (2×200 ml). The combined organic phases were dried (MgSO4) and evaporated to an oil. This oil was dissolved in ethyl acetate (400 ml) and a solution of tetrabutylammonium fluoride (1M in tetrahydrofuran, 130 ml, 130 mmol) added. After stirring at room temperature for 2 hours, water (200 ml) was added, and the two layers separated. The aqueous phase was further extracted with ethyl acetate (200 ml), the organic layers dried (MgSO4) and evaporated to give the product as an oil (50 g) which was used crude for Description 3. 1H NMR (CDCl3) δ7.53-7.55 (2H, m), 7.19-7.35 (3H, m) 5.56 (1H, s), 4.27 (2H, s), 3.99-4.03 (1H, m) 3.25 (1H, bs), 2.77-2.81 (1H, m) 2.77 (1H, bs), 2.12-2.20 (1H, m) 1.91-1.99 (2H, m), 1.77-1.83 (1H, m), 1.39 (9H, s).

Workup

  1. waitat room temperature for 2 hours
  2. temperaturebefore cooling to −10° C
  3. stirringThe reaction was stirred at room temperature overnight
  4. customquenched by addition of water/saturated aqueous ammonium chloride (200 ml/200 ml)
  5. extractionextracted with ethyl acetate (2×200 ml)
  6. dry with materialThe combined organic phases were dried (MgSO4)
  7. customevaporated to an oil
  8. dissolutionThis oil was dissolved in ethyl acetate (400 ml)
  9. stirringAfter stirring at room temperature for 2 hours
  10. customthe two layers separated
  11. extractionThe aqueous phase was further extracted with ethyl acetate (200 ml)
  12. dry with materialthe organic layers dried (MgSO4)
  13. customevaporated

Sources & evidence

ORD record
ord-c76d04b4dfb24bb7b353cce6eae135f9
Source dataset
uspto-grants-2001_05
Patent number
US06225320B1

Reaction notes

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