Pivaloyl chloride → Methyl 2-chloro-5-(pivalamidomethyl)benzoate

HRID 889539Notes

Reaction equation

HRID 889539 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:5]=[CH:6][C:7]([Cl:14])=[C:8]([CH:13]=1)[C:9]([O:11][CH3:12])=[O:10].C(N(CC)C(C)C)(C)C.[C:24](Cl)(=[O:29])[C:25]([CH3:28])([CH3:27])[CH3:26]>ClCCl>[Cl:14][C:7]1[CH:6]=[CH:5][C:4]([CH2:3][NH:2][C:24](=[O:29])[C:25]([CH3:28])([CH3:27])[CH3:26])=[CH:13][C:8]=1[C:9]([O:11][CH3:12])=[O:10]

Participants

5

Reactant 3

HCID 62493Pivaloyl chlorideHCID 81531DiisopropylethylamineHCID 66524840Methyl 5-(aminomethyl)-2-chlorobenzoate--hydrogen chloride (1/1)

Product 1

HCID 67971274Methyl 2-chloro-5-(pivalamidomethyl)benzoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a thermally controlled reactor, add methyl 5-(aminomethyl)-2-chlorobenzoate hydrochloride (700 g, 3.51 mol, 1.0 equiv), dichloromethane (4.9 L), and N,N-diisopropylethylamine (1.71 L, 9.82 mol, 2.8 equiv). Add pivaloyl chloride (515 mL, 4.21 mol, 1.2 equiv) dropwise at such a rate that the internal temperature does not exceed 21° C. Upon completion of the addition, stir the reaction mixture at room temperature for one hour. Quench the reaction mixture with saturated aqueous sodium bicarbonate (10 L). Extract the mixture with dichloromethane (2×1 L), combine the organic extracts, dry over sodium sulfate, filter, and concentrate under reduced pressure to give an oil, (1.1 kg) carried on crude without further purification. MS (m/z) (35Cl/37Cl) 284/286 (M+1)

Workup

  1. customdoes not exceed 21° C
  2. additionUpon completion of the addition
  3. customQuench the reaction mixture with saturated aqueous sodium bicarbonate (10 L)
  4. extractionExtract the mixture with dichloromethane (2×1 L)
  5. dry with materialdry over sodium sulfate
  6. filtrationfilter
  7. concentrationconcentrate under reduced pressure
  8. customto give an oil, (1.1 kg)
  9. customcarried on crude without further purification

Sources & evidence

ORD record
ord-ed7f2283204a4d09957d66ddb8023f65
Source dataset
uspto-grants-2012_08
Patent number
US08252831B2

Reaction notes

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