4-Chlorobenzaldehyde → HCID 25058431, compound

HRID 884339Notes

Reaction equation

HRID 884339 reaction equation
[NH2:1][C:2]1[C:3]2[O:10][CH:9]=[C:8]([C@H:11]3[C@:15]([CH3:17])([OH:16])[C@H:14]([OH:18])[C@@H:13]([CH2:19][OH:20])[O:12]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:21][C:22]1[CH:29]=[CH:28][C:25]([CH:26]=O)=[CH:24][CH:23]=1>C1COCC1.[Cl-].[Cl-].[Zn+2]>[NH2:1][C:2]1[C:3]2[O:10][CH:9]=[C:8]([C@H:11]3[C@:15]4([CH3:17])[O:16][CH:26]([C:25]5[CH:28]=[CH:29][C:22]([Cl:21])=[CH:23][CH:24]=5)[O:18][C@@H:14]4[C@@H:13]([CH2:19][OH:20])[O:12]3)[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

5

Reactant 2

HCID 77264-ChlorobenzaldehydeHCID 11623314HCID 11623314, compound

Product 1

HCID 25058431HCID 25058431, compoundYield 55.5%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A suspension of (2S,3R,4R,5R)-2-(4-aminofuro[3,2-d]pyrimidin-7-yl)-5-(hydroxymethyl)-3-methyl-tetrahydrofuran-3,4-diol (281 mg, 1.0 mmol) in THF (4 mL) was treated with ZnCl2 (695 mg, 98%, 5 0 mmol) and 4-chlorobenzaldehyde (1.43 g, 10.0 mmol) followed by stirring at 60° C. for 14 h. The reaction mixture was quenched with aqueous 2N NaOH (6.5 mL) followed by dilution with water (80 mL), and extraction with CHCl3 (2×100 mL). The combined organic extracts were dried over MgSO4, filtered, and concentrated. The residue was purified on a silica gel column using chloroform/MeOH (1:0 to 20:1, Rf=0.31, CHCl3/MeOH=20:1) as eluent to give 224 mg (55%) of the desired product as a white solid. 1H NMR (MeOH-d4, a mixture of diastereoisomers): δ 8.23 (s, 1H), 8.22 (s, 1H), 7.72-7.50 (m, 4H), 7.44 (s, 2H), 6.16 (s, 1H), 5.47-5.41(m, 1H), 5.31 (s, 1H), 4.53 (d, J=3.1 Hz, 1H), 4.17-4.11 (m, 1H), 3.73-3.57 (m, 2H), 1.25 (s, 3H); MS (ES+): 404.3 (M+H)+.

Workup

  1. customThe reaction mixture was quenched with aqueous 2N NaOH (6.5 mL)
  2. extractionfollowed by dilution with water (80 mL), and extraction with CHCl3 (2×100 mL)
  3. dry with materialThe combined organic extracts were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified on a silica gel column

Sources & evidence

ORD record
ord-945e9f9371ce486da4f18d556daaa35c
Source dataset
uspto-grants-2012_08
Patent number
US08242085B2

Reaction notes

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