Sodium Hydroxide → HCID 59001094, 화합물

HRID 1893851노트

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HRID 1893851 반응식
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

참가 물질

11

반응물 7

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

생성물 1

HCID 59001094HCID 59001094, 화합물수율 100%

시약·촉매·용매 3

HCID 887Methanol용매HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-2abff2f6e6a44293818deb1ec1e9a6df
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08513253B2

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