1-Propanol → HCID 15409399, compound

HRID 1784140Notes

Reaction equation

HRID 1784140 reaction equation
[C:1]([NH:9][C:10]1[CH:15]=[CH:14][N:13]([C@@H:16]2[O:24][CH2:23][C@@H:21]([OH:22])[C@@H:19]([OH:20])[C@H:17]2[OH:18])[C:12](=[O:25])[N:11]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:26](Cl)([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:27].C(O)CC>CN(C)C=O.N1C=CC=CC=1>[C:1]([NH:9][C:10]1[CH:15]=[CH:14][N:13]([C@@H:16]2[O:24][CH2:23][C@@H:21]([OH:22])[C@@H:19]([OH:20])[C@H:17]2[O:18][C:26](=[O:27])[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:12](=[O:25])[N:11]=1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 10311-PropanolHCID 7412Benzoyl chlorideHCID 15409398HCID 15409398, compound

Product 1

HCID 15409399HCID 15409399, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
124 °C

Procedure

54.0 g (0.155 mol) of N4-benzoyl-1-(β-D-ribopyranosyl)cytosine 1 were dissolved in 830 ml of dimethylformamide (DMF) and 1.5 l of pyridine (both solvents dried and stored over molecular sieve 3 Å) with warming to 124° C. 23.0 g (0.163 mol; 1.05 eq.) of BzCl, dissolved in 210 ml of pyridine, were added dropwise at −58° to −63° C. in the course of 3.5 h. The batch was stirred overnight in a cooling bath. 90.3 g (1.5 mol; 10 eq.) of n-propanol were stirred in and the batch was concentrated at 40° C. in a high vacuum. Pyridine residues were removed by twice adding 150 ml of toluene and concentrating again. 124.3 g of residue were dissolved in 500 ml of CH2Cl2, extracted twice by stirring with 300 ml of half-concentrated NaHCO3 solution each time, and the precipitated solid was filtered off and dried: 60.7 g of residue. The CH2Cl2 phase was concentrated: 25.0 g. Separate chromatography on silica gel 60 (40×10 cm) with gradients (AcOEt/isohexane, 4:1, then pure AcOEt, then AcOET/MeOH, 19:1 to 2:1) yielded (TLC (silica gel, ACOET)):

Workup

  1. dry with material1.5 l of pyridine (both solvents dried
  2. additionwere added dropwise at −58° to −63° C. in the course of 3.5 h
  3. concentrationwas concentrated at 40° C. in a high vacuum
  4. customPyridine residues were removed
  5. additionby twice adding 150 ml of toluene
  6. concentrationconcentrating again
  7. dissolution124.3 g of residue were dissolved in 500 ml of CH2Cl2
  8. extractionextracted twice
  9. stirringby stirring with 300 ml of half-concentrated NaHCO3 solution each time
  10. filtrationthe precipitated solid was filtered off
  11. customdried
  12. concentrationThe CH2Cl2 phase was concentrated
  13. customSeparate chromatography on silica gel 60 (40×10 cm) with gradients (AcOEt/isohexane, 4:1
  14. custompure AcOEt, then AcOET/MeOH, 19:1 to 2:1) yielded (TLC (silica gel, ACOET))

Sources & evidence

ORD record
ord-da4e90e4acbe4d3ca8e30de0142f42ff
Source dataset
uspto-grants-2009_03
Patent number
US07501506B2

Reaction notes

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