Pivaloyl chloride → N-(4,5-Difluoro-2-(hydroxymethyl)phenyl)pivalamide

HRID 1985528노트

반응식

HRID 1985528 반응식
[CH3:1][C:2]([CH3:7])([CH3:6])[C:3](Cl)=[O:4].[NH2:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([F:16])=[CH:11][C:10]=1[CH2:17][OH:18].CCN(C(C)C)C(C)C>C(Cl)Cl.C1COCC1>[F:16][C:12]1[C:13]([F:15])=[CH:14][C:9]([NH:8][C:3](=[O:4])[C:2]([CH3:7])([CH3:6])[CH3:1])=[C:10]([CH2:17][OH:18])[CH:11]=1

참가 물질

5

반응물 3

HCID 62493Pivaloyl chlorideHCID 81531DiisopropylethylamineHCID 21925570(2-Amino-4,5-difluorophenyl)methanol

생성물 1

HCID 59732039N-(4,5-Difluoro-2-(hydroxymethyl)phenyl)pivalamide

시약·촉매·용매 1

HCID 21919333Tetrahydrofurane dichloromethane용매

실험 절차

Trimethylacetyl chloride (4.01 mL, 32.55 mmol) was added to the solution of the crude (2-amino-4,5-difluorophenyl)methanol in CH2Cl2/THF (50 mL/10 mL) at 0° C., followed by the addition of DIEA (10.8 mL, 62 mmol). The resulting mixture was stirred for 30 min, and then partitioned between saturated NaHCO3 (100 mL) and CH2Cl2 (150 mL). After separation, the organic phase was washed with brine (40 mL), dried over MgSO4, and concentrated on rotary vacuum to afford the expected product, which was pure enough to be used in next step without further purification; 1H NMR (400 MHz, CDCl3) δ ppm 1.28 (s, 9H), 4.62 (s, 2H), 6.94 (dd, J=10.20, 8.44 Hz, 1H), 8.08 (dd, J=12.72, 7.68 Hz, 1H), 9.04 (s, 1H); Mass spec. 244.11 (MH+), Calc. for C12H15F2NO2 243.11.

후처리

  1. custompartitioned between saturated NaHCO3 (100 mL) and CH2Cl2 (150 mL)
  2. customAfter separation
  3. washthe organic phase was washed with brine (40 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated on rotary vacuum

출처 및 근거

ORD 기록
ord-215d7698488e453789f2e92ca6d19d0d
출처 데이터셋
uspto-grants-2009_06
특허 번호
US07544680B2

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