Triethylamine → Tert-butyl n-heptyl-n-[2-[4-[2-(7-trifluoromethylbenzoxazol-2-ylthio)ethyl]piperazin-1-yl]ethyl]carbamate

HRID 1064847Notes

Reaction equation

HRID 1064847 reaction equation
[CH2:1]([N:8]([CH2:16][CH2:17][N:18]1[CH2:23][CH2:22][N:21]([CH2:24][CH2:25]O)[CH2:20][CH2:19]1)[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].C(N(CC)CC)C.CS(Cl)(=O)=O.[SH:39][C:40]1[O:41][C:42]2[C:48]([C:49]([F:52])([F:51])[F:50])=[CH:47][CH:46]=[CH:45][C:43]=2[N:44]=1.C(=O)([O-])[O-].[K+].[K+]>C1COCC1.CN(C)C1C=CN=CC=1.CN(C=O)C>[CH2:1]([N:8]([CH2:16][CH2:17][N:18]1[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][S:39][C:40]2[O:41][C:42]3[C:48]([C:49]([F:52])([F:51])[F:50])=[CH:47][CH:46]=[CH:45][C:43]=3[N:44]=2)[CH2:20][CH2:19]1)[C:9](=[O:15])[O:10][C:11]([CH3:13])([CH3:14])[CH3:12])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7]

Participants

9

Reactant 5

HCID 8471Triethylamine2×HCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chloride2×HCID 22272782tert-butyl N-heptyl-N-[2-[4-(2-hydroxyethyl)piperazin-1-yl]ethyl]carbamateHCID 178506117HCID 178506117, compound

Product 1

HCID 22272608Tert-butyl n-heptyl-n-[2-[4-[2-(7-trifluoromethylbenzoxazol-2-ylthio)ethyl]piperazin-1-yl]ethyl]carbamateYield 37%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of this alcohol (500 mg, 1.35 mmol) in THF (10 ml) were added triethylamine (180 mg, 1.78 mmol) and 4-(dimethylamino) pyridine (16 mg, 0.13 mmol), and then methanesulfonyl chloride (190 mg, 1.66 mmol) was dropped there into with ice-cooling and stirred for 20 minutes. Further, to the same solution were added triethylamine (45 mg, 0.44 mmol) and methanesulfonyl chloride (45 mg, 0.39 mmol) was dropped thereinto with ice-cooling and stirred for 1 hour. The reaction solution was filtered and the filtrate was concentrated in vacuo. The resulting residue was dissolved in DMF (3 ml), and the resulting solution was dropped into a solution of 2-mercapto-7-trifluoromethylbenzoxazole (310 mg, 1.41 mmol) and potassium carbonate (280 mg, 2.03 mmol) in DMF (7 ml) and stirred at 80° C. for 90 minutes. The reaction solution was concentrated in vacuo and the resulting residue was filtered off with ether. The filtrate was concentrated in vacuo and the resulting residue was purified by a silica gel column chromatography (silica gel 35 g, developing solvent; hexane:acetone=10:1) to provide 283 mg (yield 37%) of tert-butyl N-heptyl-N-[2-[4-[2-(7-trifluoromethylbenzoxazol-2-ylthio)ethyl]piperazin-1-yl]ethyl]carbamate as pale yellow oil.

Workup

  1. temperaturecooling
  2. additionwas dropped
  3. temperaturewith ice-cooling
  4. stirringstirred for 1 hour
  5. filtrationThe reaction solution was filtered
  6. concentrationthe filtrate was concentrated in vacuo
  7. dissolutionThe resulting residue was dissolved in DMF (3 ml)
  8. stirringstirred at 80° C. for 90 minutes
  9. concentrationThe reaction solution was concentrated in vacuo
  10. filtrationthe resulting residue was filtered off with ether
  11. concentrationThe filtrate was concentrated in vacuo
  12. customthe resulting residue was purified by a silica gel column chromatography (silica gel 35 g, developing solvent; hexane:acetone=10:1)

Sources & evidence

ORD record
ord-aa8bcf8c8a7e49a0a44930246cfca2f9
Source dataset
uspto-grants-2005_11
Patent number
US06969711B2

Reaction notes

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