Oxalic Acid → 1[n-[(1,3-Benzodioxol-5-yl)sulfonyl]-n-(2-methylpropyl)amino]-3(s)-[bis(phenylmethyl)amino]-4-phenyl-2(r)-butanol

HRID 1934481Notes

Reaction equation

HRID 1934481 reaction equation
[C:1]1([CH2:7][N:8]([C@@H:16]([CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C@H:17]([OH:24])[CH2:18][NH:19][CH2:20][CH:21]([CH3:23])[CH3:22])[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(O)(=O)C(O)=O.C(=O)([O-])[O-].[K+].[K+].[O:44]1[C:48]2[CH:49]=[CH:50][C:51]([S:53](Cl)(=[O:55])=[O:54])=[CH:52][C:47]=2[O:46][CH2:45]1>O.O1CCOCC1.C(OCC)(=O)C>[O:44]1[C:48]2[CH:49]=[CH:50][C:51]([S:53]([N:19]([CH2:18][C@@H:17]([OH:24])[C@@H:16]([N:8]([CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[CH2:7][C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH2:20][CH:21]([CH3:23])[CH3:22])(=[O:54])=[O:55])=[CH:52][C:47]=2[O:46][CH2:45]1

Participants

8

Reactant 4

HCID 971Oxalic AcidHCID 11430Potassium CarbonateHCID 49134011,3-Benzodioxole-5-sulfonyl chlorideHCID 9806223N-(3(S)-[N,N-bis(phenylmethyl)amino]-2(R)-hydroxy-4-phenylbutyl]-N-isobutylamine

Product 1

HCID 113878411[n-[(1,3-Benzodioxol-5-yl)sulfonyl]-n-(2-methylpropyl)amino]-3(s)-[bis(phenylmethyl)amino]-4-phenyl-2(r)-butanolYield 105%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent2×

Procedure

To a 5000 mL, 3-necked flask fitted with a mechanical stirrer was added N-[3(S)-[N,N-bis(phenylmethyl)amino]-2(R)-hydroxy-4-phenylbutyl]-N-isobutylamine.oxalic acid salt (354.7 g, 0.7 mole) and 1,4-dioxane (2000 mL). A solution of potassium carbonate (241.9 g, 1.75 moles) in water (250 mL) was then added. The resultant heterogeneous mixture was stirred for 2 hours at room temperature followed by the addition of 1,3-benzodioxole-5-sulfonyl chloride (162.2 g, 0.735 mole) dissolved in 1,4-dioxane (250 mL) over 15 minutes. The reaction mixture was stirred at room temperature for 18 hours. Ethyl acetate (1000 mL) and water (500 mL) were charged to the reactor and stirring continued for another 1 hour. The aqueous layer was separated and further extracted with ethyl acetate (200 mL). The combined ethyl acetate layers were washed with 25% brine solution (500 mL) and dried over anhydrous magnesium sulfate. After filtering and washing the magnesium sulfate with ethyl acetate (200 mL), the solvent in the filtrate was removed under reduced pressure yielding the desired sulfonamide as an viscous yellow foamy oil (440.2 g 105% yield). HPLC/MS (electrospray) (m/z 601 [M+H]+].

Workup

  1. customTo a 5000 mL, 3-necked flask fitted with a mechanical stirrer
  2. stirringThe reaction mixture was stirred at room temperature for 18 hours
  3. stirringstirring
  4. waitcontinued for another 1 hour
  5. customThe aqueous layer was separated
  6. extractionfurther extracted with ethyl acetate (200 mL)
  7. washThe combined ethyl acetate layers were washed with 25% brine solution (500 mL)
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationAfter filtering
  10. washwashing the magnesium sulfate with ethyl acetate (200 mL)
  11. customthe solvent in the filtrate was removed under reduced pressure

Sources & evidence

ORD record
ord-ed5db9aa245f4404b1fc49d96fe889fd
Source dataset
uspto-grants-2002_05
Patent number
US06384036B1

Reaction notes

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