Sodium Hydroxide → N4-benzoyl-2'-fluoro-3'-(4-methoxytrityl)amino-2',3'-dideoxycytidine

HRID 342922Notes

Reaction equation

HRID 342922 reaction equation
[C:1]([NH:9][C:10]1[CH:53]=[CH:52][N:13]([C@@H:14]2[O:28][C@H:17]([CH2:18][O:19]C(=O)C3C=CC=CC=3)[C@@H:16]([NH:29][C:30]([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[C:31]3[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=3)[C@H:15]2[F:51])[C:12](=[O:54])[N:11]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+]>N1C=CC=CC=1.CO.O>[C:1]([NH:9][C:10]1[CH:53]=[CH:52][N:13]([C@@H:14]2[O:28][C@H:17]([CH2:18][OH:19])[C@@H:16]([NH:29][C:30]([C:45]3[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=3)([C:39]3[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=3)[C:31]3[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=3)[C@H:15]2[F:51])[C:12](=[O:54])[N:11]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 54559474N4,5'-O-dibenzoyl-2'-fluoro-3'-(4-methoxytrityl)amino-2',3'-dideoxycytidine

Product 1

HCID 56606094N4-benzoyl-2'-fluoro-3'-(4-methoxytrityl)amino-2',3'-dideoxycytidine

Reagents, catalysts & solvents 1

HCID 21976680Pyridine methanol waterSolvent2×

Procedure

N4 -benzoyl-2'-fluoro-3'-(4-methoxytrityl)amino-2',3'-dideoxycytidine 15 was prepared as follows: To 1.3 g (1.75 mmol) of 14 in 20 mL of 65/30/5 pyridine/methanol/water, cooled in an ice bath, was added 10 mL of cold 2M NaOH in 65/30/5 pyridine/methanol/water. The mixture was stirred cold for 20 min, then neutralized with pyridinium-H+ form Bio-Rad AG® 50W-X8 cation exchange resin. After 5 min, the resin was removed by filtration and washed with methanol. The combined filtrate and wash were concentrated in vacuo to an oil, which was dissolved in 100 mL ethyl acetate. The mixture was washed with 100 mL saturated aqueous NaHCO3 and with water (2×100 mL). After concentration in vacuo to a foam, the product was dissolved in 10 mL CH2Cl2 and pipetted into 75 mL rapidly stirred hexane/ether, 2/1. The product was collected by filtration and dried under vacuum, giving 1.13 g (102% yield) of product as a white powder. Mass-spectrometry, FAB+, M+Cs+, calculated: 753.1489, observed: 753.1499. 1H NMR δ 8.30 (br d, J=6.8 Hz, 1H), 7.89 (br d, J=6.7 Hz, 2H), 7.64 (dd, J=7.4, 7.4 Hz, 1H), 7.44-7.56 (mm, 9H), 7.22-7.32 (mm, 9H), 6.82 (d, J=8.8Hz, 2H), 5.80 (d, J=15.7Hz, 1H), 4.26 (mm, 2H), 4.13 (d, J=10.2 Hz, 1H), 3.81 (s, 3H), 3.26 (dddd, J=3.4, 10.7, 10.8, 26.5 Hz, 1H), 2.93 (dd, J =3.3, 50.5 Hz, 1H), 2.50 (dd, J=2.8, 11.0 Hz, 1H); 19F NMR δ -195.3 (m).

Workup

  1. customform Bio-Rad AG® 50W-X8 cation exchange resin
  2. waitAfter 5 min
  3. customthe resin was removed by filtration
  4. washwashed with methanol
  5. washThe combined filtrate and wash
  6. concentrationwere concentrated in vacuo to an oil, which
  7. dissolutionwas dissolved in 100 mL ethyl acetate
  8. washThe mixture was washed with 100 mL saturated aqueous NaHCO3 and with water (2×100 mL)
  9. concentrationAfter concentration in vacuo to a foam
  10. dissolutionthe product was dissolved in 10 mL CH2Cl2
  11. filtrationThe product was collected by filtration
  12. customdried under vacuum

Sources & evidence

ORD record
ord-75788960e3024afbb412569bc6990e87
Source dataset
uspto-grants-1999_01
Patent number
US05859233

Reaction notes

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