Acetic Anhydride → (S)-1-(4-(3-(cyclopentyloxy)-4-methoxyphenyl)-2-(pyrrolidin-1-ylmethyl)piperazin-1-yl)ethanone

HRID 1423151Notes

Reaction equation

HRID 1423151 reaction equation
Cl.Cl.[CH:3]1([O:8][C:9]2[CH:10]=[C:11]([N:17]3[CH2:22][CH2:21][NH:20][C@@H:19]([CH2:23][N:24]4[CH2:28][CH2:27][CH2:26][CH2:25]4)[CH2:18]3)[CH:12]=[CH:13][C:14]=2[O:15][CH3:16])[CH2:7][CH2:6][CH2:5][CH2:4]1.C(N(CC)CC)C.[C:36](OC(=O)C)(=[O:38])[CH3:37].C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH:3]1([O:8][C:9]2[CH:10]=[C:11]([N:17]3[CH2:22][CH2:21][N:20]([C:36](=[O:38])[CH3:37])[C@@H:19]([CH2:23][N:24]4[CH2:25][CH2:26][CH2:27][CH2:28]4)[CH2:18]3)[CH:12]=[CH:13][C:14]=2[O:15][CH3:16])[CH2:7][CH2:6][CH2:5][CH2:4]1

Participants

6

Reactant 4

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 131732229(S)-1-(3-(cyclopentyloxy)-4-methoxyphenyl)-3-(pyrrolidin-1-ylmethyl)piperazine, dihydrochloride2×

Product 1

HCID 52918895(S)-1-(4-(3-(cyclopentyloxy)-4-methoxyphenyl)-2-(pyrrolidin-1-ylmethyl)piperazin-1-yl)ethanoneYield 65%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (S)-1-(3-(cyclopentyloxy)-4-methoxyphenyl)-3-(pyrrolidin-1-ylmethyl)piperazine, dihydrochloride (Example 40, Compound 128) (108 mg, 0.25 mmol) in CH2Cl2 (5 mL) at 0-5 C was treated with triethylamine (105 uL, 0.75 mmol) followed by acetic anhydride (51 uL, 0.50 mmol). The reaction mixture was allowed to warm to room temperature and stir 16 h. After this time the reaction mixture was treated with a saturated aqueous solution of NaHCO3 (2 mL). The organic portion was then dried over MgSO4, filtered, and evaporated to afford quenched with evaporated and the residue purified by silica gel flash chromatography with 100% EtOAc then 10% MeOH/EtOAc as eluant to afford product as an oil (65 mg, 65%). LC/MS (Method B) 2.22 min, [M+1]+ 402. Potency class C.

Workup

  1. dry with materialThe organic portion was then dried over MgSO4
  2. filtrationfiltered
  3. customevaporated
  4. customto afford
  5. customquenched
  6. customwith evaporated
  7. customthe residue purified by silica gel flash chromatography with 100% EtOAc

Sources & evidence

ORD record
ord-4b996566ad954fd4a3ce331b9106f0f0
Source dataset
uspto-grants-2015_01
Patent number
US08927546B2

Reaction notes

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