Water → HCID 135978869, compound

HRID 1516286Notes

Reaction equation

HRID 1516286 reaction equation
[C:1]([O:9][CH2:10][C@@H:11]1[C:15]([O:17][C:18](=[O:20])[CH3:19])([CH3:16])[C@:14]([F:22])([CH3:21])[CH:13]([N:23]2[CH:31]=[N:30][C:29]3[C:24]2=[N:25][CH:26]=[N:27][C:28]=3Cl)[O:12]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.NCC1CC1.[OH2:39]>C(O)C>[C:1]([O:9][CH2:10][C@@H:11]1[C:15]([O:17][C:18](=[O:20])[CH3:19])([CH3:16])[C@:14]([F:22])([CH3:21])[CH:13]([N:23]2[CH:31]=[N:30][C:29]3[C:28](=[O:39])[NH:27][CH:26]=[N:25][C:24]2=3)[O:12]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 962WaterHCID 81671(Cyclopropylmethyl)ammonium chlorideHCID 86634317HCID 86634317, compound

Product 1

HCID 135978869HCID 135978869, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a stirred solution of ((2R,4R)-3-acetoxy-5-(6-chloro-9H-purin-9-yl)-4-fluoro-3,4-dimethyl-tetrahydrofuran-2-yl)methyl benzoate (about 0.55 g, 1.19 mmol) in ethanol (about 15 ml) was added aminomethyl cyclopropane hydrochloride (about 1.50 g, 14.2 mmol) at room temperature and refluxed for about 24 hours. Completion of the reaction monitored by thin-layer chromatography, water added to the reaction mixture and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulphate, Concentration under reduced pressure and purification by silica gel column chromatography using 3% methanol in dichloromethane as eluent furnished title compound (0.4 g) as a colorless solid. Yield: 67%; 1H NMR (300 MHz, CDCl3): δ 12.74 (bs, 1H), 8.16 (s, 1H), 8.06-8.03 (m, 3H), 7.65-7.50 (t, 1H), 7.48-7.45 (m, 2H), 7.47-7.42 (m, 2H), 6.45 (d, 1H, J=22.5 Hz), 4.84-4.78 (m, 2H), 4.47-4.45 (m, 1H), 2.18 (s, 3H), 1.90 (s, 3H), 1.44 (d, 3H, J=22.8 Hz), 1.19-1.08 (m, 1H), 0.59-0.55 (m, 2H), 0.34-0.31 (m, 2H); ES Mass: [M+1]+ 445 (20%), [M+Na] 467 (45%); IR cm−: 3431, 2920, 1746, 1726, 1588, 1372, 1278, 1113, 1094, 950, 829; HPLC: 98%.

Workup

  1. temperaturerefluxed for about 24 hours
  2. additionadded to the reaction mixture
  3. extractionthe aqueous layer was extracted with ethyl acetate
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulphate, Concentration under reduced pressure and purification by silica gel column chromatography

Sources & evidence

ORD record
ord-117c270228474a7da0f3910a089179b4
Source dataset
uspto-grants-2012_07
Patent number
US08227431B2

Reaction notes

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