Pivaloyl chloride → 2-Chloro-5-[(2,2-dimethylpropanamido)methyl]benzoic acid

HRID 1846076Notes

Reaction equation

HRID 1846076 reaction equation
[ClH:1].[NH2:2][CH2:3][C:4]1[CH:5]=[CH:6][C:7](C)=[C:8]([CH:12]=1)[C:9]([OH:11])=[O:10].FC(F)(F)C(=N[Si](C)(C)C)O[Si](C)(C)C.[C:29](Cl)([C:31]([CH3:34])([CH3:33])[CH3:32])=[O:30]>C1COCC1>[Cl:1][C:7]1[CH:6]=[CH:5][C:4]([CH2:3][NH:2][C:29]([C:31]([CH3:34])([CH3:33])[CH3:32])=[O:30])=[CH:12][C:8]=1[C:9]([OH:11])=[O:10]

Participants

5

Reactant 3

HCID 62493Pivaloyl chlorideHCID 94358Bis(trimethylsilyl)trifluoroacetamideHCID 671161835-Aminomethyl-2-methyl-benzoic acid hydrochloride (1:1)

Product 1

HCID 584832082-Chloro-5-[(2,2-dimethylpropanamido)methyl]benzoic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A mixture of 5-(aminomethyl)-2-methylbenzoic acid hydrochloride (3.2 g, 14 mmol), BSTFA (2.26 mL, 14 mmol) and 50 mL THF was heated to reflux for 1 h and cooled to 0° C. 10 mL of TEA were added, followed by 1.77 mL (14 mmol) Piv-Cl in 50 mL THF. The mixture was stirred overnight at rt, concentrated i.vac., diluted with water and acidified with 22 mL glacial acetic acid. After 30 min it was extracted 3× with DCM, the organic phase was dried with Na2SO4, concentrated i.vac and purified via MPLC. Yield: 2.57 g (66%). MS [M+H]+=270 (Cl-isotope pattern); HPLC: Rt=4.09 min (Method MC-2).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 1 h
  3. concentrationconcentrated i.vac
  4. addition, diluted with water
  5. extractionAfter 30 min it was extracted 3× with DCM
  6. dry with materialthe organic phase was dried with Na2SO4
  7. concentrationconcentrated i.vac
  8. custompurified via MPLC

Sources & evidence

ORD record
ord-aa70e18e381741eba05338a9f9e0fc2e
Source dataset
uspto-grants-2015_02
Patent number
US08951999B2

Reaction notes

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