4-Phenylbutyric Acid → HCID 22141231, compound

HRID 1826512Notes

Reaction equation

HRID 1826512 reaction equation
[C:1]1([CH2:7][CH2:8][CH2:9][C:10]([OH:12])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH3:36][C:37]1([C:43]2[CH:44]=[C:45]([NH:49][S:50]([CH3:53])(=[O:52])=[O:51])[CH:46]=[CH:47][CH:48]=2)[CH:42]2[CH:38]1[CH2:39][NH:40][CH2:41]2.C(=O)([O-])O.[Na+]>CN(C)C=O>[CH3:36][C:37]1([C:43]2[CH:44]=[C:45]([NH:49][S:50]([CH3:53])(=[O:52])=[O:51])[CH:46]=[CH:47][CH:48]=2)[CH:42]2[CH:38]1[CH2:39][N:40]([C:10](=[O:12])[CH2:9][CH2:8][CH2:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[CH2:41]2

Participants

7

Reactant 5

HCID 47754-Phenylbutyric AcidHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 22141143N-[3-(6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenyl)methanesulfonamide

Product 1

HCID 22141231HCID 22141231, compoundYield 98.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-phenylbutanoic acid (219 mg, 1.33 mmol) in N,N-dimethylformamide (20 ml) was added 1-hydroxybenzotriazole monohydrate (225 mg, 1.48 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (382 mg, 1.98 mmol). After stirring at room temperature for 15 min the mixture was treated with the hydrochloride salt of N-[3-(6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenyl]methanesulfonamide (Preparation 53, 449 mg, 1.48 mmol) and sodium hydrogen carbonate (225 mg, 2.7 mmol). The reaction mixture was stirred at room temperature for overnight before concentrating in vacuo. Water (15 ml) was added and the reaction mixture was extracted with ethyl acetate (20, 15 ml). The combined organic extracts were washed with water (15 ml), dried (MgSO4), filtered and concentrated in vacuo to give a colourless oil (540 mg). This was purified by chromatography using a Biotage Flash 12™ cartridge packed with silica gel (8 g) eluting with hexane:ethyl acetate (100:0 to 0:100 over 30 min) and then with ethyl acetate:methanol (100:0 to 0:100 over 5 min) to afford the title compound as a colourless glass (360 mg, 59%).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for overnight
  2. concentrationbefore concentrating in vacuo
  3. additionWater (15 ml) was added
  4. extractionthe reaction mixture was extracted with ethyl acetate (20, 15 ml)
  5. washThe combined organic extracts were washed with water (15 ml)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-637354b814ff4933a2906ebfb127e7ae
Source dataset
uspto-grants-2006_05
Patent number
US07049444B2

Reaction notes

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