2'-Deoxy-2-fluoroadenosine → 5'-O-(4,4'-Dimethoxytrityl)-2'-deoxy-2-fluoroadenosine

HRID 566697

Reaction equation

HRID 566697 reaction equation
[F:1][C:2]1[N:3]=[C:4]([NH2:19])[C:5]2[N:6]=[CH:7][N:8]([C:17]=2[N:18]=1)[C@@H:9]1[O:16][C@H:13]([CH2:14][OH:15])[C@@H:11]([OH:12])[CH2:10]1.CO[C:22]1[C:23](OC)=[C:24]([CH:39]=[CH:40][CH:41]=1)[C:25](Cl)([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[C:44](OCC)(=[O:46])C.[CH3:50][OH:51]>N1C=CC=CC=1>[CH3:44][O:46][C:29]1[CH:30]=[CH:31][C:26]([C:25]([O:15][CH2:14][C@H:13]2[O:16][C@@H:9]([N:8]3[C:17]4[N:18]=[C:2]([F:1])[N:3]=[C:4]([NH2:19])[C:5]=4[N:6]=[CH:7]3)[CH2:10][C@@H:11]2[OH:12])([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:24]2[CH:39]=[CH:40][C:41]([O:51][CH3:50])=[CH:22][CH:23]=2)=[CH:27][CH:28]=1

Participants

5

Reactant 3

HCID 4478642'-Deoxy-2-fluoroadenosineHCID 21584119Ethylacetate methanolHCID 66624882Dimethoxytrityl chloride

Product 1

HCID 206390295'-O-(4,4'-Dimethoxytrityl)-2'-deoxy-2-fluoroadenosine

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

2′-deoxy-2-fluoroadenosine (20, 12 g, 0.45 mol) and dimethoxytrityl chloride (18.1 g, 0.53 mol) were dissolved in anhydrous pyridine (100 mL) and stirred at ambient temperature until the trace amount of the starting material remaining matched the bis DMT impurity forming (3 h) as monitored by TLC (Rf 0.20, starting material; Rf 0.60, product; Rf 0.85, bis DMT product, ethyl acetate-methanol 9:1). The reaction was quenched by the addition of methanol (50 mL) and then concentrated under reduced pressure to an oil. The residue was partitioned between ethyl acetate (250 mL) and sat'd sodium bicarbonate (250 mL). The aqueous layer was extracted with ethyl acetate (100 mL) once more and the combined extracts were concentrated under reduced pressure. The resulting oil was purified by silica gel chromatography (400 g) using a gradient of methanol in ethyl acetate (0-5%). The appropriate fractions were combined, concentrated under reduced pressure, coevaporated with anhydrous acetonitrile (200 mL) and dried (1 mm Hg, 25° C., 24 h) to a foam, 23.2 g (90%). The product can be crystallized from dichloromethane to give white crystals, mp 239-243° C. H-NMR (DMSO-d6) d 2.2-2.4 and 2.7-2.9 (m, 2, 2′-CH2), 3.18 (m, 2, 5′-H and 5″-H), 3.75 (s, 6, O—CH3), 3.98 (m, 1, 4′-H), 4.43 (m, 1, 3′-H), 5.38 (d, 1, 3′-OH), 6.15 (t, 1, 1′-H), 6.83 (m, 4, arom.), 7.15-7.4 (m, 9, arom.), 7.83 (br s, 2, NH2), 8.23 (s, 1, 8-H). F-NMR (DMSO-d6) δ-53.5 (s).

Workup

  1. customforming (3 h)
  2. customThe reaction was quenched by the addition of methanol (50 mL)
  3. concentrationconcentrated under reduced pressure to an oil
  4. customThe residue was partitioned between ethyl acetate (250 mL) and sat'd sodium bicarbonate (250 mL)
  5. extractionThe aqueous layer was extracted with ethyl acetate (100 mL) once more
  6. concentrationthe combined extracts were concentrated under reduced pressure
  7. customThe resulting oil was purified by silica gel chromatography (400 g)
  8. concentrationconcentrated under reduced pressure
  9. customdried (1 mm Hg, 25° C., 24 h) to a foam, 23.2 g (90%)
  10. customThe product can be crystallized from dichloromethane
  11. customto give white crystals, mp 239-243° C

Sources & evidence

ORD record
ord-eee807ae55c0488ba05ffdce5be9ccde
Source dataset
uspto-grants-2001_01
Patent number
US06175004B1

Linked notes

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