Phosphoric Acid → Disodium

HRID 1174417Notes

Reaction equation

HRID 1174417 reaction equation
[CH2:1]([C@H:8]([NH:42][C:43]([C@@H:45]([NH:50][C:51](=[O:54])[O:52][CH3:53])[C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[C@@H:9]([O:38][CH2:39]SC)[CH2:10][C@@H:11]([NH:25][C:26](=[O:37])[C@H:27]([C:33]([CH3:36])([CH3:35])[CH3:34])[NH:28][C:29]([O:31][CH3:32])=[O:30])[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=2)=[CH:15][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[P:55](=[O:59])([OH:58])([OH:57])[OH:56].IN1C(=O)CCC1=O.C(=O)([O-])[O-].[Na+:72].[Na+:73]>O1CCCC1.CO>[CH3:53][O:52][C:51](=[O:54])[NH:50][C@@H:45]([C:46]([CH3:47])([CH3:48])[CH3:49])[C:43](=[O:44])[NH:42][C@@H:8]([CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C@@H:9]([O:38][CH2:39][O:57][P:55]([OH:59])([OH:58])=[O:56])[CH2:10][C@H:11]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=2)=[CH:15][CH:14]=1)[NH:25][C:26](=[O:37])[C@H:27]([C:33]([CH3:35])([CH3:34])[CH3:36])[NH:28][C:29](=[O:30])[O:31][CH3:32].[Na:72][Na:73]

Participants

8

Reactant 4

HCID 1004Phosphoric AcidHCID 10340Sodium CarbonateHCID 120273N-IodosuccinimideHCID 91275847HCID 91275847, compound

Product 2

HCID 141233DisodiumYield 56%HCID 11216603HCID 11216603, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of Example 204A (2.46 mg, 3.2 mmol) in tetrahydrofuran (16.0 mL) was treated with 4 Å molecular sieves (8.0 g), a solution of phosphoric acid (32.0 mL, 0.5 M in DMF), and N-iodosuccinimide (1.45 g, 6.4 mmol) at 25° C. for 45 minutes. The mixture was poured into cold 10% sodium carbonate, diluted with methanol, filtered and through celite. The filtrate was decolorized with saturated sodium thiosulfate and concentrated. The resulting concentrate was dissolved in methanol, filtered and concentrated. Methanol and water were added to the resulting concentrate and the pH was adjusted to 9 by addition of 10% Na2CO3, and the mixture was purified by reverse phase HPLC using a C18 column, eluting with a gradient starting with water and ending with methanol, to give the title compound as a disodium salt (1.53 g, 56% yield). 1H NMR (300 MHz, MeOH-d4), δ ppm 0.80 (s, 9 H), 0.88 (s, 9 H), 1.67-1.76 (m, 1H), 2.00-2.10 (m, 1 H), 2.68-2.99 (m, 4 H), 3.54 (s, 3 H), 3.65 (s, 3 H), 3.70-3.74 (m, 1 H), 3.93 (s, 1 H), 3.94 (s, 1 H), 4.22-4.32 (m, 1 H), 4.34-4.38 (m, 1 H), 5.02 (dd, J=8.8, 5.5 Hz, 1 H), 5.15 (dd, J=8.8, 5.2 Hz, 1 H), 7.05-7.33 (m, 8 H), 7.77-7.89 (m, 4 H), 8.56 (m, 1 H).

Workup

  1. filtrationfiltered and through celite
  2. concentrationconcentrated
  3. concentrationThe resulting concentrate
  4. dissolutionwas dissolved in methanol
  5. filtrationfiltered
  6. concentrationconcentrated
  7. additionMethanol and water were added to the resulting
  8. concentrationconcentrate
  9. additionthe pH was adjusted to 9 by addition of 10% Na2CO3
  10. customthe mixture was purified by reverse phase HPLC
  11. washeluting with a gradient

Sources & evidence

ORD record
ord-acb536f28ba14470b0eec919758618ad
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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