Benzoyl chloride → HCID 67482197, compound

HRID 1817757Notes

Reaction equation

HRID 1817757 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:11]=[CH:10][C:9]([CH:12]([NH:14][NH:15][C:16]([O:18]C(C)(C)C)=O)[CH3:13])=[CH:8][CH:7]=1)=[O:5])[CH3:2].C(O)(C(F)(F)F)=O.C(Cl)Cl.C(Cl)(=O)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C(C1C=C(C)C=C(C(C)(C)C)N=1)(C)(C)C>C(Cl)Cl>[C:16]([NH:15][NH:14][C@@H:12]([C:9]1[CH:8]=[CH:7][C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])=[CH:11][CH:10]=1)[CH3:13])(=[O:18])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1

Participants

6

Reactant 4

HCID 7412Benzoyl chlorideHCID 988982,6-Di-tert-butyl-4-methylpyridineHCID 21863450Trifluoroacetic acid methylene chlorideHCID 67482189tert-Butyl 2-{1-[4-(ethoxycarbonyl)phenyl]ethyl}hydrazine-1-carboxylate

Product 1

HCID 67482197HCID 67482197, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

Thus the slow moving enantiomer tert-butyl 2-{1-[4-(ethoxycarbonyl)phenyl]ethyl}hydrazinecarboxylate (0.74 g, 2.42 mmol) from a chiral separation as described above was treated with TFA/CH2Cl2 (1:1, 10 mL) for 1 h at r.t. The reaction was concentrated on a rotovap and the residual TFA was removed by co-evaporation from toluene. The resulting ethyl 4-(1-hydrazinoethyl)benzoate was then dissolved in CH2Cl2 (15 mL) and cooled to −78° C. A solution of benzoyl chloride (365 μL, 3.15 mmol) and 2,6-di-tert-butyl-4-methylpyridine (745 mg, 3.63 mmol) in CH2Cl2 (5 mL) was added slowly at −78° C. After 3 h at −78° C., the reaction mixture was loaded quickly on a SiO2 column and eluted with 30% EtOAc/hexane. Fractions containing product were concentrated and purified further on HPLC using Kromasil C8 column (10% to 70% CH3CN/H2O/0.1% TFA, 12 min), and again on silica gel column (30% EtOAc/Hexane) to give (R)-(+)-ethyl 4-[1-(2-benzoylhydrazino)ethyl]benzoate. HPLC/MS: m/z=313.3 (M+1)+, Rt=3.08 min. Daicel column Chiralcel OJ, 40° C., 0.5 mL/min, 10% isopropanol/90% n-heptane: t 35.79 min; [α]D20=+192.4° (cl, CHCl3); 1H NMR (500 MHz, CDCl3): δ 8.03 (2H, d, J=8.0 Hz), 7.94 (1H, br s), 7.66 (2H, d, J=7.5 Hz), 7.51 (1H, t, J=7.5 Hz), 7.54 (2H, d, J=8.0 Hz), 7.40 (2H, t, J=8.0 Hz), 4.39 (2H, q, J=7.0 Hz), 4.36 (1H, q, J=7.0 Hz), 1.46 (3H, d, J=6.0 Hz), 1.41 (3H, t, J=7.0 Hz); 13C NMR (500 MHz, CDCl3): δ 167.76, 166.69, 148.16, 132.70, 132.27, 130.21, 130.18, 128.94, 127.47, 127.15, 61.22, 60.21, 21.21, 14.58. (S)-(−)-ethyl 4-[1-(2-benzoylhydrazino)ethyl]-benzoate was similarly prepared from the faster moving isomer of tert-butyl 2-{1-[4-(ethoxycarbonyl)phenyl]ethyl}hydrazinecarboxylate. HPLC/MS: m/z=313.4 (M+1)+, Rt=3.09 min. Daicel column Chiralcel OJ, 40° C., 0.5 mL/min, 10% isopropanol/90% n-heptane: t 34.99 min; [α]D20=−194.4° (cl, CHCl3); 1H NMR (500 MHz, CDCl3): δ 8.02 (2H, d, J=8.0 Hz), 7.73 (1H, br s), 7.65 (2H, d, J=8.0 Hz), 7.49 (1H, t, J=8.0 Hz), 7.48 (2H, d, J=8.0 Hz), 7.39 (2H, t, J=8.0 Hz), 4.38 (2H, q, J=7.0 Hz), 4.34 (1H, q, J=7.0 Hz), 1.44 (3H, d, J=6.5 Hz), 1.41 (3H, t, J=7.0 Hz); 13C NMR (500 MHz, CDCl3): δ 167.81, 166.74, 148.73, 132.92,132.15, 130.13, 130.02, 128.90, 127.43, 127.12, 61.20, 60.09, 21.52, 14.58.

Workup

  1. concentrationThe reaction was concentrated on a rotovap
  2. customthe residual TFA was removed by co-evaporation from toluene
  3. dissolutionThe resulting ethyl 4-(1-hydrazinoethyl)benzoate was then dissolved in CH2Cl2 (15 mL)
  4. washeluted with 30% EtOAc/hexane
  5. additionFractions containing product
  6. concentrationwere concentrated
  7. custompurified further on HPLC
  8. customKromasil C8 column (10% to 70% CH3CN/H2O/0.1% TFA, 12 min)

Sources & evidence

ORD record
ord-574883b6d581430bb5c159fc55e75326
Source dataset
uspto-grants-2009_10
Patent number
US07598285B2

Reaction notes

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