Lithium borohydride → (1-(2-(Trimethylsilyl)ethylsulfonyl)piperidin-3-yl)methanol

HRID 1254193Notes

Reaction equation

HRID 1254193 reaction equation
[CH3:1][Si:2]([CH3:20])([CH3:19])[CH2:3][CH2:4][S:5]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([C:14](OCC)=[O:15])[CH2:9]1)(=[O:7])=[O:6].[Li+].[BH4-]>C1COCC1>[CH3:1][Si:2]([CH3:20])([CH3:19])[CH2:3][CH2:4][S:5]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([CH2:14][OH:15])[CH2:9]1)(=[O:7])=[O:6]

Participants

4

Reactant 2

HCID 4148881Lithium borohydride2×HCID 59383013Ethyl 1-(2-(trimethylsilyl)ethanesulfonyl)piperidine-3-carboxylate

Product 1

HCID 59383010(1-(2-(Trimethylsilyl)ethylsulfonyl)piperidin-3-yl)methanolYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Ethyl 1-(2-(trimethylsilyl)ethanesulfonyl)piperidine-3-carboxylate (9.00 g, 28 mol) was dissolved in THF (200 mL) in a three-neck 500 mL flask and cooled to 0° C. A solution of LiBH4 (2.0 M in THF, 28 mL, 0.056 mol, 2.0 equiv) was added via addition funnel. The mixture was allowed to warm to rt and stir for 15 h. Significant amounts of the starting ester remained; an additional charge of the LiBH4 solution (28 mL, 0.056 mol) was added and the mixture stirred for an additional 17 h. After this period analysis by LC-MS showed consumption of the starting ester. The mixture was cooled to 0° C. and the excess LiBH4 was quenched by dropwise addition of MeOH (100 mL). The volatile materials were removed and the residue partitioned between ether (100 mL) and 1.0 M aq HCl (100 mL). The layers were separated and the aqueous layer extracted with additional ether (3×50 mL). The combined organic extracts were washed with brine and dried over Na2SO4. The clear solution was evaporated to yield (1-(2-(trimethylsilyl)ethylsulfonyl)piperidin-3-yl)methanol (5.25 g, 67%) as a white solid which was of sufficient purity to use in the next step. 1H NMR (CDCl3) δ 0.00 (s, 9H), 0.95 (m, 2H), 1.21 (m, 1H), 1.5-8 (m, 5H), 2.75-2.82 (m, 3H), 2.91 (t of d, 1H), 3.53 (m, 2H), 3.62 (d of d, 1H).

Workup

  1. temperatureto warm to rt
  2. additionwas added
  3. stirringthe mixture stirred for an additional 17 h
  4. waitAfter this period analysis by LC-MS showed
  5. customconsumption of the starting ester
  6. temperatureThe mixture was cooled to 0° C.
  7. customthe excess LiBH4 was quenched by dropwise addition of MeOH (100 mL)
  8. customThe volatile materials were removed
  9. customthe residue partitioned between ether (100 mL) and 1.0 M aq HCl (100 mL)
  10. customThe layers were separated
  11. extractionthe aqueous layer extracted with additional ether (3×50 mL)
  12. washThe combined organic extracts were washed with brine
  13. dry with materialdried over Na2SO4
  14. customThe clear solution was evaporated

Sources & evidence

ORD record
ord-3bc253c629f54124a6b8208a32f5356e
Source dataset
uspto-grants-2013_06
Patent number
US08455521B2

Reaction notes

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