Triethylamine → HCID 66672731, compound

HRID 423665Notes

Reaction equation

HRID 423665 reaction equation
CS(Cl)(=O)=O.O[CH2:7][CH:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][CH:17]([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]1.C(N(CC)CC)C.[Br:27][C:28]1[CH:33]=[CH:32][C:31]([SH:34])=[CH:30][CH:29]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O>[Br:27][C:28]1[CH:33]=[CH:32][C:31]([S:34][CH2:7][CH:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][CH:17]([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[CH:30][CH:29]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 660494-BromothiophenolHCID 57930058HCID 57930058, compound

Product 1

HCID 66672731HCID 66672731, compoundYield 26.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Methanesulfonyl chloride (0.28 mL, 3.6 mmol) was added dropwise to a solution of 1-methylethyl 4-(hydroxymethyl)-1-piperidinecarboxylate (prepared as in Example 9, Step 1, 600 mg, 3 mmol), triethylamine (0.627 mL, 4.5 mmol), and CH2—Cl2 (10 mL) at 0° C. The mixture was stirred at 0° C. for 30 min, then at ambient temperature for 2 h. The mixture was washed with water, and the organics were concentrated. The resulting crude material was mixed with 4-bromobenzenethiol (567 mg, 3 mmol) and K2CO3 (829 mg, 6 mmol) in DMF (10 mL), and the mixture was stirred at ambient temperature overnight. The mixture was charged with water, and extracted with EtOAc. The organics were dried over MgSO4, filtered, and the filtrate was concentrated. The crude product was purified by chromatography on a silica gel column using 0 to 10% EtOAc/hexanes to give 292 mg (26%) of 1-methylethyl 4-{[(4-bromophenyl)thio]methyl}-1-piperidinecarboxylate as a clear oil. 1H NMR (400 MHz, CDCl3): δ 7.37 (d, 2H, J=8.5 Hz), 7.15 (d, 2H, J=8.5 Hz), 4.95-4.82 (m, 1H), 4.15-4.09 (m, 2H), 2.80 (d, 2H, J=6.9 Hz), 2.72-2.60 (m, 2H), 1.85-1.77 (m, 2H), 1.70-1.60 (m, 1H), 1.24-1.08 (m, 8H); LRMS (ESI), m/z 372/374 (M+H).

Workup

  1. waitat ambient temperature for 2 h
  2. washThe mixture was washed with water
  3. concentrationthe organics were concentrated
  4. stirringthe mixture was stirred at ambient temperature overnight
  5. extractionextracted with EtOAc
  6. dry with materialThe organics were dried over MgSO4
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated
  9. customThe crude product was purified by chromatography on a silica gel column

Sources & evidence

ORD record
ord-006902ee08c4415e9a4547afa3ed273b
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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