Sodium Hydroxide → HCID 59001094, compound

HRID 1893851Notes

Reaction equation

HRID 1893851 reaction equation
C([O:3][C:4](=O)[CH:5]([NH:11][S:12]([C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=1)(=[O:14])=[O:13])[CH2:6][C:7]([F:10])([CH3:9])[CH3:8])C.[OH-].[Na+].ClC1C=CC(S([NH:35]C(CC(F)(C)C)C(O)=O)(=O)=O)=CC=1.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[Cl-].[NH4+].Cl.CN(C)CCCN=C=NCC>CO.O.CN(C=O)C>[Cl:21][C:18]1[CH:19]=[CH:20][C:15]([S:12]([NH:11][CH:5]([CH2:6][C:7]([F:10])([CH3:9])[CH3:8])[C:4]([NH2:35])=[O:3])(=[O:14])=[O:13])=[CH:16][CH:17]=1

Participants

11

Reactant 7

HCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 59432819HCID 59432819, compoundHCID 67196650HCID 67196650, compound

Product 1

HCID 59001094HCID 59001094, compoundYield 100%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 2-(4-chlorobenzenesulfonylamino)-4-fluoro-4-methyl-pentanoic acid ethyl ester (457 mg, 1.30 mmol) in MeOH (20 mL) was treated with 10 N NaOH (780 μL, 7.8 mmol) at rt for 18 h. The crude reaction mixture was concentrated in vacuo. The residue was treated with water (50 mL) and 1 N HCl (20 mL). The aqueous solution was extracted with EtOAc (3×100 mL). The combined organic layers were washed with brine (50 mL), dried over MgSO4, filtered and concentrated in vacuo to afford a white solid containing 2-(4-chlorobenzenesulfonylamino)-4-fluoro-4-methyl-pentanoic acid. A mixture of the crude solid, 1-hydroxybenzotriazole (263 mg, 1.95 mmol), diisopropylethylamine (670 mg, 5.2 mmol), ammonium chloride (140 mg, 2.6 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (373 mg, 1.95 mmol), and DMF (20 mL) was stirred at rt for 24 h. The crude mixture was poured into water (500 mL). The aqueous solution was extracted with EtOAc/hexane (90:10, 3×150 mL). The combined organic layers were washed with brine (50 mL), dried over MgSO4, filtered and concentrated in vacuo. The crude concentrate was purified using silica gel column chromatography (95:5, chloroform/MeOH) to afford 0.426 g (100% yield) of the title compound: LCMS (M+Na)+345.3; 1H NMR (400 MHz, DMSO-d6) δ 8.10 (d, 1H, J=9.2), 7.77 (d, 2H, J=8.5), 7.62 (d, 2H, J=8.9), 7.34 (s, 1H), 6.92 (s, 1H). 3.85 (m, 1H), 1.89 (m, 1H), 1.74 (m, 1H), 1.31 (d, 3H, J=21.7), 1.29 (d, 3H, J=21.9).

Workup

  1. customThe crude reaction mixture
  2. concentrationwas concentrated in vacuo
  3. additionThe residue was treated with water (50 mL) and 1 N HCl (20 mL)
  4. extractionThe aqueous solution was extracted with EtOAc (3×100 mL)
  5. washThe combined organic layers were washed with brine (50 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto afford a white solid
  10. extractionThe aqueous solution was extracted with EtOAc/hexane (90:10, 3×150 mL)
  11. washThe combined organic layers were washed with brine (50 mL)
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. concentrationThe crude concentrate
  16. customwas purified

Sources & evidence

ORD record
ord-2abff2f6e6a44293818deb1ec1e9a6df
Source dataset
uspto-grants-2013_08
Patent number
US08513253B2

Reaction notes

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