Methanol → Phenstatin Acetate

HRID 496228Notes

Reaction equation

HRID 496228 reaction equation
[C:1]([O:4]C(=O)C)(=[O:3])[CH3:2].[CH3:8][O:9][C:10]1[CH:11]=[CH:12][C:13]([C:17]([C:19]2[CH:20]=[C:21]([O:29][CH3:30])[C:22]([O:27][CH3:28])=[C:23]([O:25][CH3:26])[CH:24]=2)=[O:18])=[CH:14][C:15]=1[OH:16].C(N(CC)CC)C.CO>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:8][O:9][C:10]1[CH:11]=[CH:12][C:13]([C:17]([C:19]2[CH:24]=[C:23]([O:25][CH3:26])[C:22]([O:27][CH3:28])=[C:21]([O:29][CH3:30])[CH:20]=2)=[O:18])=[CH:14][C:15]=1[OH:16].[C:1]([O-:4])(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 887MethanolHCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 9948888Phenstatin

Product 1

HCID 86759841Phenstatin Acetate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Acetic anhydride (74 μL, 0.79 mmol) was added to a solution of phenstatin (3b, 0.2 g, 0.63 mmol), DMAP (7.8 mg, 0.063 mmol) and triethylamine (0.13 mL, 0.94 mmol) in dry methylene chloride (1.5 mL, under argon at room temperature). The yellow solution was stirred for 30 min (reaction was complete by TLC). Methanol (5 Ml) was added and the reaction mixture concentrated to a solid that was washed with diethyl ether (3 ×10 mL) and partitioned between ethyl acetate and cold Ln hydrochloric acid. The organic layer was washed with 10% aqueous sodium bicarbonate and dried. Solvent removed, in vacuo, gave an off-white solid that was recrystallized from ethyl acetate-hexane to give colorless snowflakes of analytical purity: EIMS m/z (peak height) 360 M+, 60%), 318 (100%), 303 (10%), 195 (20%), 151 (30%), 91 (32%), 44 (25%). 1H-NMR (CDCl3)δ H 7.740 (1H, dd, J6/2 2.1 Hz, J6/5 8.1 Hz, H-6). 7.556 (1H, d, J2/6 2.1 Hz, H-2), 7.026 (1H, d, J5/6 8.0 Hz, H-5), 7.013 (2H, s, H-2′, 6′), 3.914 (3H, s, 4-OCH3), 3.907 (3H, s, 4′-OCH3), 3.863 (6H, s, 3′, 5′-OCH3), 2.315 (3H, s, —OCOCH3).

Workup

  1. custom(reaction was complete by TLC)
  2. concentrationthe reaction mixture concentrated to a solid
  3. washthat was washed with diethyl ether (3 ×10 mL)
  4. custompartitioned between ethyl acetate and cold Ln hydrochloric acid
  5. washThe organic layer was washed with 10% aqueous sodium bicarbonate
  6. customdried
  7. customSolvent removed, in vacuo
  8. customgave an off-white solid
  9. customthat was recrystallized from ethyl acetate-hexane
  10. customto give colorless snowflakes of analytical purity

Sources & evidence

ORD record
ord-047a20263ceb4b9bb1e7157a4a00eabd
Source dataset
uspto-grants-2005_09
Patent number
US06943194B1

Reaction notes

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