Citric Acid → HCID 21877522, compound

HRID 724363Notes

Reaction equation

HRID 724363 reaction equation
[OH-].[K+].O.CO.[CH3:6][O:7][C:8]1[CH:9]=[C:10]([CH:16]=[CH:17][C:18]2[C:26]3[C:21](=[CH:22][C:23]([C:27]4[CH:32]=[CH:31][C:30]([O:33][CH2:34][O:35][CH3:36])=[C:29]([O:37][CH3:38])[CH:28]=4)=[CH:24][CH:25]=3)[N:20](S(C3C(C)=CC(C)=CC=3C)(=O)=O)[N:19]=2)[CH:11]=[CH:12][C:13]=1[O:14][CH3:15].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1>[CH3:6][O:7][C:8]1[CH:9]=[C:10](/[CH:16]=[CH:17]/[C:18]2[C:26]3[C:21](=[CH:22][C:23]([C:27]4[CH:32]=[CH:31][C:30]([O:33][CH2:34][O:35][CH3:36])=[C:29]([O:37][CH3:38])[CH:28]=4)=[CH:24][CH:25]=3)[NH:20][N:19]=2)[CH:11]=[CH:12][C:13]=1[O:14][CH3:15]

Participants

6

Reactant 4

HCID 311Citric AcidHCID 14797Potassium Hydroxide2×HCID 22242641Methanol--water (1/1)HCID 69370229HCID 69370229, compound

Product 1

HCID 21877522HCID 21877522, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
30 °C

Procedure

A 1M solution of KOH (1.0 g, 17.8 mmol) in 1:1 water/MeOH (18 mL total) was prepared under argon and was degassed by vacuum/purge cycles with argon (5 times). In a separate flask, 3-[2-(3,4-dimethoxy-phenyl)-vinyl]-6-(3-methoxy-4-methoxymethoxy-phenyl)-1-(2,4,6-trimethyl-benzenesulfonyl)-1H-indazole (289 mg, 0.461 mmol, 1.0 equiv) was dissolved in THF (8 mL) under argon. To this solution was added the above 1M KOH solution (10 mL, 1:1 water/MeOH). The reaction was warmed to 30° C. and was allowed to stir for 7 h. The reaction mix was neutralized by the addition of 20% citric acid (7 mL). The resulting mix was partitioned between ethyl acetate (150 mL) and water (100 mL). The organic material was separated, dried over sodium sulfate, decanted, and concentrated under reduced pressure to give cis and trans 3-[2-(3,4-dimethoxy-phenyl)-vinyl]-6-(3-methoxy-4-methoxymethoxy-phenyl)-1H-indazole (used crude): Rf sm 0.46, p1 0.17, p2 0.23 (ethyl acetate-hexane 1:1); 1H NMR cis isomer (CDCl3) δ 7.55 (s, 1H), 7.3–7.1 (m, 6H), 7.02 (dd, 1H, J=1.9, 8.3 Hz), 6.85 (d, 1H, J=12.5 Hz), 6.78 (d, 1H, J=12.5 Hz), 6.74 (d, 1H, J=8.3 Hz), 5.21 (s, 2H), 3.88 (s, 3H), 3.70 (s, 3H), 3.43 (s, 3H), 3.42 (s, 3H). MS (ES) [m+H]/z Calc'd 447. found 447. [m−H]/z Calc'd 445. found 445.

Workup

  1. customwas degassed
  2. customby vacuum/purge cycles with argon (5 times)
  3. additionThe reaction mix
  4. additionThe resulting mix
  5. customwas partitioned between ethyl acetate (150 mL) and water (100 mL)
  6. customThe organic material was separated
  7. dry with materialdried over sodium sulfate
  8. customdecanted
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-72951ebf013449dcbbaad421925e6a28
Source dataset
uspto-grants-2006_11
Patent number
US07141587B2

Reaction notes

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