Triethylamine → HCID 178461555, compound

HRID 915811Notes

Reaction equation

HRID 915811 reaction equation
[Cl:1][C:2]1[CH:28]=[CH:27][C:5]([O:6][CH2:7][C:8]([N:10]2[CH2:15][C@H:14]([CH2:16]O)[N:13]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[CH2:12][C@H:11]2[CH3:26])=[O:9])=[CH:4][CH:3]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.[NH:41]1[CH:45]=[N:44][N:43]=[N:42]1>C(Cl)Cl>[Cl:1][C:2]1[CH:28]=[CH:27][C:5]([O:6][CH2:7][C:8]([N:10]2[CH2:15][C@@H:14]([CH2:16][C:45]3[NH:44][N:43]=[N:42][N:41]=3)[N:13]([CH2:18][C:19]3[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=3)[CH2:12][C@H:11]2[CH3:26])=[O:9])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 11441144(2R,5R)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl4-(4-fluorobenzyl)-5-((hydroxy)methyl)piperazineHCID 178418441HCID 178418441, compound

Product 1

HCID 178461555HCID 178461555, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (2R,5R)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)-5-((hydroxy)methyl)piperazine (0.17 g, 0.42 mmol) in CH2Cl2 (50 mL) at 0° C. was added triethylamine (excess) and methane sulfonyl chloride (0.050 mL, 0.5 mmol). The resultant mixture was stirred at 0° C. until consumption of alcohol was observed by TLC analysis. The mixture was concentrated of volatiles in vacuo. Residue was taken up in anhydrous DMF (5 mL) and K2CO3 (excess) added, followed by tetrazole (0.050 g, 0.71 mmol). The resulting mixture was stirred at ambient temperature for 3 days and filtered. The filtrate was concentrated in vacuo and the residue taken up in ethyl acetate. This was washed with water then brine, then dried over MgSO4 and concentrated in vacuo to afford a yellow oil. Purification, by flash column chromatography on silica gel afforded 25 mg of (2R,5R)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)-5-((tetrazolyl)methyl)piperazine as a white solid: NMR (CDCl3) 7.3 (m, 5), 7.0 (m, 4), 4.8-4.1 (m, 5), 3.8 (m, 3), 3.2 (m, 2), 2.8 (dd, 1), 2.5 (dd, 1), 1.4 (d, 3) ppm, MS (ESI) 458.

Workup

  1. concentrationThe mixture was concentrated of volatiles in vacuo
  2. additionK2CO3 (excess) added
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated in vacuo
  5. washThis was washed with water
  6. dry with materialbrine, then dried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customto afford a yellow oil
  9. customPurification

Sources & evidence

ORD record
ord-d42e00fdb8c844189bd55dbcfa273602
Source dataset
uspto-grants-2007_09
Patent number
US07268140B2

Reaction notes

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