p-(Chlorodiphenylmethyl)anisole → N4,5'-O-dibenzoyl-2'-fluoro-3'-(4-methoxytrityl)amino-2',3'-dideoxycytidine

HRID 342921Notes

Reaction equation

HRID 342921 reaction equation
[C:1]([NH:9][C:10]1[CH:32]=[CH:31][N:13]([C@@H:14]2[O:28][C@H:17]([CH2:18][O:19][C:20](=[O:27])[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C@@H:16]([NH2:29])[C@H:15]2[F:30])[C:12](=[O:33])[N:11]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:34][O:35][C:36]1[CH:55]=[CH:54][C:39]([C:40](Cl)([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)=[CH:38][CH:37]=1>N1C=CC=CC=1>[C:1]([NH:9][C:10]1[CH:32]=[CH:31][N:13]([C@@H:14]2[O:28][C@H:17]([CH2:18][O:19][C:20](=[O:27])[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C@@H:16]([NH:29][C:40]([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[C:39]3[CH:38]=[CH:37][C:36]([O:35][CH3:34])=[CH:55][CH:54]=3)[C@H:15]2[F:30])[C:12](=[O:33])[N:11]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 84462p-(Chlorodiphenylmethyl)anisoleHCID 54409373N4,5'-O-dibenzoyl-2'-fluoro-3'-amino-2',3'-dideoxycytidine

Product 1

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

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

N4,5'-O-dibenzoyl-2'-fluoro-3'-(4-methoxytrityl)amino-2',3'-dideoxycytidine 14 was prepared as follows: To 0.9 g (2.0 mmol) of 13 in 25 mL anhydrous pyridine was added 0.86 g (2.8 mmol) 4-methoxytrityl chloride, and the mixture stirred overnight. The reaction was quenched with 0.5 mL H2O and concentrated in vacuo. CH2Cl2 (50 mL) was added and washed with 50 mL saturated aqueous NaHCO3 and with water (2×50 mL). The solvent was removed in vacuo, replaced with 10 mL CH2Cl2, and pipetted into 80 mL rapidly stirred 1/1 hexane/ether. After further stirring for 2 h, the product was collected by filtration and dried under vacuum, giving 1.3 g (88% yield) of product as a white powder. Mass-spectrometry, FAB+, M+H+, calculated: 725.2775, observed: 725.2761. 1H NMR δ 8.59 (br s, 1H), 8.07 (br d, J=5.7 Hz, 1H), 7.89 (br d, J=7 Hz, 2H), 7.83 (dd, J=1.3, 6.7 Hz, 2H), 7.68 (dd, J=7.4, 7.4 Hz, 2H), 7.5-7.6 (m, 8H), 7.43 (dd, J=2.1, 6.9 Hz, 2H), 7.1-7.3 (mm, 7H), 6.71 (d, J=8.9 Hz, 2H), 5.80 (d, J=15.4 Hz, 1H), 5.03 (dd, J=2.0, 13.0 Hz, 1H), 4.98 (dd, J=2.3;, 13.1 Hz, 1H),4.41 (brd,J=10.5 Hz, 1H),3.63 (s,3H),3.36(dddd,J=3.1, 11.1, 11.1, 25.7 Hz, 1H), 2.84 (dd, J=3.1, 49.9 Hz, 1H), 2.52 (dd, J=2.7, 11.5 Hz, 1H); 19F NMR δ -196.3 (m).

Workup

  1. customThe reaction was quenched with 0.5 mL H2O
  2. concentrationconcentrated in vacuo
  3. additionCH2Cl2 (50 mL) was added
  4. washwashed with 50 mL saturated aqueous NaHCO3 and with water (2×50 mL)
  5. customThe solvent was removed in vacuo
  6. stirringrapidly stirred 1/1 hexane/ether
  7. stirringAfter further stirring for 2 h
  8. filtrationthe product was collected by filtration
  9. customdried under vacuum

Sources & evidence

ORD record
ord-5cb618d15bf143c8a5f4e8343e3eb66b
Source dataset
uspto-grants-1999_01
Patent number
US05859233

Reaction notes

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