Pivaloyl chloride → N-(2-Bromo-5-fluorophenyl)pivalamide

HRID 1985523Notes

Reaction equation

HRID 1985523 reaction equation
[CH3:1][C:2]([CH3:7])([CH3:6])[C:3](Cl)=[O:4].[Br:8][C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=1[NH2:16].CCN(C(C)C)C(C)C>C(Cl)Cl>[Br:8][C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=1[NH:16][C:3](=[O:4])[C:2]([CH3:7])([CH3:6])[CH3:1]

Participants

5

Reactant 3

HCID 62493Pivaloyl chlorideHCID 81531DiisopropylethylamineHCID 27733172-Bromo-5-fluoroaniline

Product 1

HCID 59731998N-(2-Bromo-5-fluorophenyl)pivalamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trimethylacetyl chloride (4.2 mL, 34.1 mL) was fast dropwise added to a solution of 2-bromo-5-fluorobenzenamine (4.31 g, 22.7 mmol) in CH2Cl2 (50 mL) at room temperature, followed by the addition of DIEA (7.9 mL, 45.4 mmol). The resulting mixture was stirred at room temperature for 2 hrs, and then partitioned between HCl (1N, 200 mL) and EtOAc (250 mL). After separation, the organic phase was washed with brine (50 mL), dried on MgSO4, concentrated on rotary vacuum, and purified on flash chromatography eluting with 20˜40% EtOAc/hexanes (1200 mL) to afford the expected product, as a colorless oil (6.07 g, 98% yield); 1H NMR (400 MHz, CDCl3) δ ppm 1.33 (s, 9H), 6.69 (ddd, J=8.81, 7.55, 3.02 Hz, 1H), 7.45 (dd, J=8.81, 5.79 Hz, 1H), 8.04 (s, 1H), 8.28 (dd, J=11.08, 3.02 Hz, 1H); Mass spec. 274.04 (MH+), Calc. for C11H13BrFNO 273.02.

Workup

  1. custompartitioned between HCl (1N, 200 mL) and EtOAc (250 mL)
  2. customAfter separation
  3. washthe organic phase was washed with brine (50 mL)
  4. customdried on MgSO4
  5. concentrationconcentrated on rotary vacuum
  6. custompurified on flash chromatography
  7. washeluting with 20˜40% EtOAc/hexanes (1200 mL)

Sources & evidence

ORD record
ord-ab6701fc4891424db5f4c259977f9c8d
Source dataset
uspto-grants-2009_06
Patent number
US07544680B2

Reaction notes

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