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

HRID 132379Notes

Reaction equation

HRID 132379 reaction equation
[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

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 21919333Tetrahydrofurane dichloromethaneSolvent

Procedure

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, 9 H), 4.62 (s, 2 H), 6.94 (dd, J=10.20, 8.44 Hz, 1 H), 8.08 (dd, J=12.72, 7.68 Hz, 1 H), 9.04 (s, 1 H); Mass spec. 244.11 (MH+), Calc. for C12H15F2NO2 243.11.

Workup

  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

Sources & evidence

ORD record
ord-869d6c1009ad4b3d88e39ee55f2745b5
Source dataset
uspto-grants-2008_06
Patent number
US07384931B2

Reaction notes

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