Boron trifluoride etherate → Methyl 4-(1-aminocyclopropyl)benzoate

HRID 1694375

Reaction equation

HRID 1694375 reaction equation
[C:1]([C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:5][CH:4]=1)#[N:2].[CH3:13][CH2:14][Mg+].[Br-].B(F)(F)F.CCOCC>C1(C)C=CC=CC=1.C1COCC1>[NH2:2][C:1]1([C:3]2[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:5][CH:4]=2)[CH2:14][CH2:13]1

Participants

6

Reactant 3

HCID 8000Boron trifluoride etherateHCID 70791Methyl 4-cyanobenzoateHCID 178461630HCID 178461630, compound

Product 1

HCID 45140209Methyl 4-(1-aminocyclopropyl)benzoateYield 43%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Methyl 4-cyanobenzoate (2.6 kg, 16.1 mol) was dissolved in 40 L of toluene at −25° C. and Ti(Oi-Pr)4 (4.73 L, 16.1 mol) was added over 5 min, followed by EtMgBr (10.5 L of a 3.07M solution in THF, 32.3 mol) over 2 hr. After aging for 30 min, BF3.OEt2 (4.1 L, 32 mol) was added over 40 min and the mixture was aged for another 40 min. The reaction was quenched by the addition of 40 L of 3N HCl. The layers were separated and the aqueous layer was washed with 13 L toluene. The aqueous layer was then extracted with 2-MeTHF (2×26 L and 2×13 L). The combined 2-MeTHF layers were washed with 3N NaOH and the pH of the NaOH layer adjusted to 9 before separation of the layers. The organic layer was washed with 13 L of brine. Yield=43%. 1H NMR (500 MHz, CDCl3): δ 8.00 (d, 2H), 7.35 (d, 2H), 3.95 (s, 3H), 1.25 (t, 2H), 1.10 (t, 2H).

Workup

  1. customover 2 hr
  2. waitthe mixture was aged for another 40 min
  3. customThe reaction was quenched by the addition of 40 L of 3N HCl
  4. customThe layers were separated
  5. washthe aqueous layer was washed with 13 L toluene
  6. extractionThe aqueous layer was then extracted with 2-MeTHF (2×26 L and 2×13 L)
  7. washThe combined 2-MeTHF layers were washed with 3N NaOH
  8. customthe pH of the NaOH layer adjusted to 9 before separation of the layers
  9. washThe organic layer was washed with 13 L of brine

Sources & evidence

ORD record
ord-2b4be886d5c54c15811377e8cb9bff9f
Source dataset
uspto-grants-2012_04
Patent number
US08158671B2

Linked notes

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