Triethylamine → 1-[(4-Fluorophenyl)carbamoyl]cyclopropanecarboxylic Acid

HRID 331211

Reaction equation

HRID 331211 reaction equation
C(N(CC)CC)C.[C:8]1([C:14]([OH:16])=[O:15])([C:11](O)=[O:12])[CH2:10][CH2:9]1.S(Cl)(Cl)=O.[F:21][C:22]1[CH:28]=[CH:27][C:25]([NH2:26])=[CH:24][CH:23]=1>C1COCC1.C(OC(C)C)(=O)C>[F:21][C:22]1[CH:28]=[CH:27][C:25]([NH:26][C:11]([C:8]2([C:14]([OH:16])=[O:15])[CH2:10][CH2:9]2)=[O:12])=[CH:24][CH:23]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 97314-FluoroanilineHCID 24386Thionyl ChlorideHCID 690171,1-Cyclopropanedicarboxylic acid

Product 1

HCID 210815301-[(4-Fluorophenyl)carbamoyl]cyclopropanecarboxylic Acid

Reagents, catalysts & solvents 2

HCID 7915Isopropyl AcetateSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Triethylamine (8.0 kg) was added to a cooled (approximately 4° C.) solution of commercially available cyclopropane-1,1-dicarboxylic acid (2 1, 10.0 kg) in THF (63.0 kg) at a rate such that the batch temperature did not exceed 10° C. The solution was stirred for approximately 30 minutes, and then thionyl chloride (9.0 kg) was added, keeping the batch temperature below 10° C. When the addition was complete, a solution of 4-fluoroaniline (9.0 kg) in THF (25.0 kg) was added at a rate such that the batch temperature did not exceed 10° C. The mixture was stirred for approximately 4 hours and then diluted with isopropyl acetate (87.0 kg). This solution was washed sequentially with aqueous sodium hydroxide (2.0 kg dissolved in 50.0 L of water), water (40.0 L), and aqueous sodium chloride (10.0 kg dissolved in 40.0 L of water). The organic solution was concentrated by vacuum distillation followed by the addition of heptane, which resulted in the precipitation of solid. The solid was recovered by centrifugation and then dried at approximately 35° C. under vacuum to afford the title compound. (10.0 kg).

Workup

  1. customdid not exceed 10° C
  2. customthe batch temperature below 10° C
  3. additionWhen the addition
  4. customdid not exceed 10° C
  5. stirringThe mixture was stirred for approximately 4 hours
  6. washThis solution was washed sequentially with aqueous sodium hydroxide (2.0 kg dissolved in 50.0 L of water), water (40.0 L), and aqueous sodium chloride (10.0 kg dissolved in 40.0 L of water)
  7. concentrationThe organic solution was concentrated by vacuum distillation
  8. additionfollowed by the addition of heptane, which
  9. customresulted in the precipitation of solid
  10. customThe solid was recovered by centrifugation
  11. customdried at approximately 35° C. under vacuum

Sources & evidence

ORD record
ord-c64e03bd05b84d9196c0f21d60263dc3
Source dataset
uspto-grants-2014_11
Patent number
US08877776B2

Linked notes

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