Dichloromethane → (3R)-3-((benzyloxy)methyl)-1-(2-thiophenylsulfonyl)piperazine

HRID 1972335Notes

Reaction equation

HRID 1972335 reaction equation
Cl.Cl.[CH2:3]([O:10][CH2:11][C@H:12]1[CH2:17][NH:16][CH2:15][CH2:14][NH:13]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C(Cl)Cl.C(N(CC)CC)C.[S:28]1[CH:32]=[CH:31][CH:30]=[C:29]1[S:33](Cl)(=[O:35])=[O:34]>O>[CH2:3]([O:10][CH2:11][C@@H:12]1[NH:13][CH2:14][CH2:15][N:16]([S:33]([C:29]2[S:28][CH:32]=[CH:31][CH:30]=2)(=[O:35])=[O:34])[CH2:17]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 855182-Thiophenesulfonyl chlorideHCID 66582378(R)-2-(benzyloxymethyl)piperazine dihydrochloride

Product 1

HCID 70655680(3R)-3-((benzyloxy)methyl)-1-(2-thiophenylsulfonyl)piperazineYield 68.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

A 1-L round-bottomed flask was charged with (R)-2-(benzyloxymethyl)piperazine dihydrochloride (55.5 g, 199 mmol) and 300 mL of CH2Cl2. After cooling to 0° C., triethylamine (111 mL, 795 mmol) and 2-thiophenesulfonyl chloride (36.3 g, 199 mmol, Sigma-Aldrich, St. Louis, Mo.) were added. This mixture was stirred at 0° C. for 30 min and then diluted with water. The organics were separated, dried (MgSO4), filtered and concentrated to give a brown oil. Purification via column chromatography on silica gel (25 to 100% EtOAc in hexanes) gave (3R)-3-((benzyloxy)methyl)-1-(2-thiophenylsulfonyl)piperazine (47.8 g) as a light-brown solid.

Workup

  1. customThe organics were separated
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a brown oil
  6. customPurification via column chromatography on silica gel (25 to 100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-1cc8b2582e0240f0acad23712f51b834
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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