Iodine → (6S)-5,6,7,8-tetrahydrofolic acid

HRID 2226992Notes

Reaction equation

HRID 2226992 reaction equation
II.CO.[OH-].[Na+].SCCO.[C:11]([OH:42])(=[O:41])[CH2:12][CH2:13][C@H:14]([NH:18][C:19]([C:21]1[CH:40]=[CH:39][C:24]([NH:25][CH2:26][CH:27]2[NH:38][C:37]3[C:35](=[O:36])[NH:34][C:32]([NH2:33])=[N:31][C:30]=3[NH:29][CH2:28]2)=[CH:23][CH:22]=1)=[O:20])[C:15]([OH:17])=[O:16].C(O)(=O)CC[C@H](NC(C1C=CC(NCC2CNC3N=C(NC(C=3N=2)=O)N)=CC=1)=O)C(O)=O.C1C(C(NC(C([O-])=O)CCC([O-])=O)=O)=CC=C(N)C=1.C1N(C2C=CC(C(=O)N[C@H](C(O)=O)CCC(O)=O)=CC=2)CC2N1C1C(=O)NC(N)=NC=1NC2>Cl>[C:11]([OH:42])(=[O:41])[CH2:12][CH2:13][C@H:14]([NH:18][C:19]([C:21]1[CH:22]=[CH:23][C:24]([NH:25][CH2:26][C@@H:27]2[NH:38][C:37]3[C:35](=[O:36])[NH:34][C:32]([NH2:33])=[N:31][C:30]=3[NH:29][CH2:28]2)=[CH:39][CH:40]=1)=[O:20])[C:15]([OH:17])=[O:16]

Participants

10

Reactant 8

HCID 807IodineHCID 887MethanolHCID 15672-MercaptoethanolHCID 14798Sodium HydroxideHCID 5103842p-Aminobenzoyl glutamateHCID 135398604Dihydrofolic AcidHCID 1354001855,10-Methylene-5,6,7,8-tetrahydrofolic acidHCID 135444742Tetrahydrofolic acid

Product 1

HCID 135398650(6S)-5,6,7,8-tetrahydrofolic acid

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Conditions

Temperature
27 °C

Procedure

A solution of crude XVIb (1.34 mmol) in 30 mL 0.01M HCl was cooled to 18° C., and 33 mL of 50 mM I2 in MeOH (1.65 mmol) was added over 10 s with good stirring, with a consequent increase in temperature to 27° C. After 2.0 min, the mixture was cooled within 2.7 min to -20° C. This temperature was maintained during subsequent titration to pH 9.2 (measured without dilution) with 10M NaOH over a period of 1.5 min. The reaction was rapidly warmed to 0° C., and at the same time sparged vigorously with argon. After 3.0 min at 0° C., 58 mL of 0.1M Na2S2O4 (freshly dissolved in deaerated water) was added all at once with stirring, followed 2.0 min later by 0.82 mL 2-mercaptoethanol (11.7 mmol). Analysis by cation exchange HPLC indicated 0.74 mmol of tetrahydrofolic acid (55%). Contaminating impurities included small amounts of 7,8-dihydrofolic acid (XXIIIb), XIXb (λmax =290 nm, pH 3.0), PABA-glu, and trace N5,N10-methylene-tetrahydrofolic acid, with 74% of the 285 nm absorbance area located in the peak of desired product.

Workup

  1. temperaturethe mixture was cooled within 2.7 min to -20° C
  2. temperatureThe reaction was rapidly warmed to 0° C.
  3. customat the same time sparged vigorously with argon
  4. waitAfter 3.0 min at 0° C.
  5. dissolution58 mL of 0.1M Na2S2O4 (freshly dissolved in deaerated water)
  6. additionwas added all at once

Sources & evidence

ORD record
ord-ea44cc19e74140029be85e0c38fd0682
Source dataset
uspto-grants-1994_09
Patent number
US05350851

Reaction notes

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