Hydrochloric Acid → 5'-Deoxy-5-fluoro-n4-(phytanyloxycarbonyl) cytidine

HRID 1910410Notes

Reaction equation

HRID 1910410 reaction equation
C([O:4][C@@H:5]1[C@H:9]([O:10]C(=O)C)[C@@H:8]([CH3:14])[O:7][C@H:6]1[N:15]1[CH:45]=[C:44]([F:46])[C:19]([NH:20][C:21]([O:23][CH2:24][CH2:25][CH:26]([CH3:43])[CH2:27][CH2:28][CH2:29][CH:30]([CH3:42])[CH2:31][CH2:32][CH2:33][CH:34]([CH3:41])[CH2:35][CH2:36][CH2:37][CH:38]([CH3:40])[CH3:39])=[O:22])=[N:18][C:16]1=[O:17])(=O)C.[OH-].[Na+].Cl>CO>[F:46][C:44]1[C:19]([NH:20][C:21]([O:23][CH2:24][CH2:25][CH:26]([CH3:43])[CH2:27][CH2:28][CH2:29][CH:30]([CH3:42])[CH2:31][CH2:32][CH2:33][CH:34]([CH3:41])[CH2:35][CH2:36][CH2:37][CH:38]([CH3:40])[CH3:39])=[O:22])=[N:18][C:16](=[O:17])[N:15]([CH:45]=1)[C@@H:6]1[O:7][C@H:8]([CH3:14])[C@@H:9]([OH:10])[C@H:5]1[OH:4]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 675449462',3'-Di-O-acetyl-5'-deoxy-5-fluoro-N4-(3,7,11,15-Tetramethyl-hexadecyl oxycarbonyl)cytidine

Product 1

HCID 675345535'-Deoxy-5-fluoro-n4-(phytanyloxycarbonyl) cytidineYield 67.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
4 °C

Procedure

The obtained crude compound 7a (16.70 g, 24.89 mmol) was dissolved in MeOH (50 ml) and cooled down on an ice bath. NaOH (24 ml, 8M) solution was added dropwise to maintain the reaction temperature at 4° C. Then the pH of the reaction mixture was immediately adjusted to 7 by dropwise addition of HCl solution (2.3M). The organic layer was separated and washed with water, dried over anhydrous Na2SO4 and filtered. The filtrate was evaporated to dryness under reduced pressure. The residue was further purified by silica column chromatography using hexane-ethyl acetate from 60:40 to 0:100 with 10% increment as the eluent. The pure title compound (9.6 g, 67.7% yield) was obtained as a waxy solid with light yellow colour. 1H NMR(CDCl3): δ0.83, 0.85, 0.86, 0.88 (4s, 12H, CH3), 0.91 (d, 3H, J=6.1 Hz, CH3), 0.95-1.84 (m, 28H, CH2+CH+OH), 1.40 (d, 3H, J=6.4 Hz, H-5), 3.91 (t, 1H, H-3), 4.15-4.38 (m, 4H, COOCH2+H-2+H-4), 5.69 (d, 1H, J=4.2 Hz, H-1), 7.79 (br s, 1H, N—CH═C—F). MS (APCI): MW: 570.21. 13C NMR(CDCl3, 100 MHz): δ [19.64, 19.71, 22.59, 22.68, 24.27, 24.30, 24.45, 24.77, 27.93, 29.68, 32.76, 35.45, 35.54, 37.25, 37.30, 37.38, 37.42, 37.48, 39.33](CH3+CH2+CH+C5), 65.33 (OCH2), [74.94, 75.12 (br), 80.75](C2,C3,C4), 92.00 (br)(C1), 124.3-128.0 (br), 135.0-138.0 (br), 153.11 (NHCOO). Elemental Analysis: calculated: C, 63.24; H, 9.20; N, 7.38; F, 3.30. Found: C, 63.59; H, 9.32; N, 7.11; F, 3.29.

Workup

  1. temperaturecooled down on an ice bath
  2. customThe organic layer was separated
  3. washwashed with water
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. customThe filtrate was evaporated to dryness under reduced pressure
  7. customThe residue was further purified by silica column chromatography

Sources & evidence

ORD record
ord-394be2e358a24e109c95832aa4ab4758
Source dataset
uspto-grants-2013_12
Patent number
US08603999B2

Reaction notes

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