Ethanol → HCID 86629020, compound

HRID 1671422Notes

Reaction equation

HRID 1671422 reaction equation
[O:1]=[C:2]1[C:6]2C=CC=CC=2C(=O)[N:3]1[CH2:12][CH2:13][CH2:14][S:15]([O:18][CH2:19][C:20]([CH3:36])([CH3:35])[C@@H:21]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:22]([O:24][CH2:25][CH3:26])=[O:23])(=[O:17])=[O:16].C(O)C.NN.C(OC(=O)C)(=O)C>C(OCC)(=O)C>[C:2]([NH:3][CH2:12][CH2:13][CH2:14][S:15]([O:18][CH2:19][C:20]([CH3:35])([CH3:36])[C@@H:21]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:22]([O:24][CH2:25][CH3:26])=[O:23])(=[O:17])=[O:16])(=[O:1])[CH3:6]

Participants

6

Reactant 4

HCID 702EthanolHCID 7918Acetic AnhydrideHCID 9321HydrazineHCID 86629019HCID 86629019, compound

Product 1

HCID 86629020HCID 86629020, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Adapting procedures or variations thereof according to Duncan et al., J. Org. Chem. 2001, 66, 5237-5240; Shue et al., Bioorg. Med. Chem. Lett. 1996, 6, 1709-1714; and Khan, J. Org. Chem. 1995, 60, 4536-4541, a 100 mL round-bottomed flask was charged with ethyl (2R)-4-{[3-(1,3-dioxobenzo[c]azolin-2-yl)propyl]sulfonyloxy}-3,3-dimethyl-2-(phenylmethoxy)butanoate (22a) (1.4 g, 2.7 mmol) and 20 mL of a mixture of ethanol (EtOH)/ethyl acetate (EtOAc) (1:1 v/v). Hydrazine (N2H4) (ca. 0.17 mL, 0.17 g, 5.4 mmol) was added at room temperature. The reaction was monitored by LC/MS. Upon completion of the reaction, acetic anhydride (Ac2O) (1.02 mL, 1.1 g, 10.8 mmol) was added to the mixture. The solution was diluted with ethyl acetate and washed with a saturated aqueous solution of sodium hydrogencarbonate (NaHCO3). The organic layer was washed with brine, dried over anhydrous magnesium sulfate (MgSO4), filtered, and the solvents removed under reduced pressure using a rotary evaporator. The crude product was purified by silica gel column chromatography using a mixture of ethyl acetate (EtOAc) and methanol (MeOH) (EtOAc/MeOH=19:1) as eluent to provide 0.8 g (69% yield) of the title compound (22b) as a colorless oil. Rf=0.50 (EtOAc/MeOH=19:1). 1H NMR (400 MHz, CDCl3): δ=1.06 (s, 3H), 1.07 (s, 3H), 1.32 (t, J=6.8 Hz, 3H), 2.00-2.06 (m, 2H), 2.05 (s, 3H), 3.08-3.12 (m, 2H), 3.35 (q, J=6.4 Hz, 2H), 3.83 (s, 1H), 3.97 (d, J=9.2 Hz, 1H), 4.17 (d, J=9.2 Hz, 1H), 4.21-4.27 (m, 2H), 4.36 (d, J=11.2 Hz, 1H), 4.62 (d, J=11.2 Hz, 1H), 5.82-5.86 (br. m, 1H), 7.26-7.35 (m, 5H), ppm. MS (ESI) m/z 430.02 (M+H)+. The analytical data was consistent with the proposed structure.

Workup

  1. additionwas added to the mixture
  2. washwashed with a saturated aqueous solution of sodium hydrogencarbonate (NaHCO3)
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate (MgSO4)
  5. filtrationfiltered
  6. customthe solvents removed under reduced pressure
  7. customa rotary evaporator
  8. customThe crude product was purified by silica gel column chromatography
  9. additiona mixture of ethyl acetate (EtOAc) and methanol (MeOH) (EtOAc/MeOH=19:1) as eluent

Sources & evidence

ORD record
ord-4b7bc2be2d224fc98e3ec63e32240539
Source dataset
uspto-grants-2011_08
Patent number
US07994218B2

Reaction notes

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