Sodium hydride → HCID 53785514, compound

HRID 1459728Notes

Reaction equation

HRID 1459728 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][SH:7])=[CH:4][CH:3]=1.[H-].[Na+].Br[CH:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]1>CN(C=O)C>[C:22]([O:21][C:19]([N:16]1[CH2:17][CH2:18][CH:13]([S:7][CH2:6][C:5]2[CH:8]=[CH:9][C:2]([F:1])=[CH:3][CH:4]=2)[CH2:14][CH2:15]1)=[O:20])([CH3:25])([CH3:23])[CH3:24]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 85171p-Fluorotoluene-alpha-thiolHCID 15541517tert-Butyl 4-bromopiperidine-1-carboxylate

Product 1

HCID 53785514HCID 53785514, compoundYield 34.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred solution of 4-fluorobenzyl mercaptan (23.34 g, 164 mmol) in DMF (150ml) under argon, cooled in a bath at -2° C. as added portionwise 60% NaH in oil (6.57 g, 164 mmol) over 12 minutes. The mixture was then stirred at room temperature for 15 minutes before recooling in bath at -2° C. and adding by cannular, over 13 minutes, a solution of 4-bromo-1(tert-butoxycarbonyl)piperidine (10.84 g, 41.0 mmol) in DMF (50ml). The mixture was then stirred at room temperature for 24 h before partitioning between water (500ml) and diethyl ether (500ml). The aqueous layer was reextracted with more diethyl ether (500ml) and the combined organic extracts were dried (MgSO4) and evaporated in vacuo. The residue was purified by flash chromatography (silica gel, 10-15% EtOAc/hexane) to give 4.58 g (34%) of the title compound as a colourless oil. δH (360 MHz, CDCl3) 1.45 (9H, s), 1.49 (2H, m), 1.86 (2H, m), 2.67 (1H, m), 2.88 (2H, m), 3.73 (2H, s), 3.92 (2H, m), 6.99 (2H, t, J=8.6 Hz), 7.28 (2H, m). m/e (ES+) 326 (M+H)+.

Workup

  1. custombefore recooling in bath at -2° C.
  2. additionadding by cannular, over 13 minutes
  3. stirringThe mixture was then stirred at room temperature for 24 h
  4. custombefore partitioning between water (500ml) and diethyl ether (500ml)
  5. dry with materialthe combined organic extracts were dried (MgSO4)
  6. customevaporated in vacuo
  7. customThe residue was purified by flash chromatography (silica gel, 10-15% EtOAc/hexane)

Sources & evidence

ORD record
ord-5b6a44f6569e47c8ac64d8543a12d6f7
Source dataset
uspto-grants-1998_12
Patent number
US05854268

Reaction notes

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