2,2-Dimethoxypropane → ((3aR,4R,6R,6aS)-6-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methanol

HRID 1054521Notes

Reaction equation

HRID 1054521 reaction equation
[Cl:1][C:2]1[C:3]2[CH:10]=[CH:9][N:8]([C@@H:11]3[CH2:15][C@H:14]([CH2:16][OH:17])[C@@H:13]([OH:18])[C@H:12]3[OH:19])[C:4]=2[N:5]=[CH:6][N:7]=1.CO[C:22](OC)([CH3:24])[CH3:23].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>>[Cl:1][C:2]1[C:3]2[CH:10]=[CH:9][N:8]([C@H:11]3[C@@H:12]4[O:19][C:22]([CH3:24])([CH3:23])[O:18][C@@H:13]4[C@@H:14]([CH2:16][OH:17])[CH2:15]3)[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

5

Reactant 4

HCID 64952,2-DimethoxypropaneHCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 86666112(1R,2S,3R,5R)-3-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)cyclopentane-1,2-diol

Product 1

HCID 76844447((3aR,4R,6R,6aS)-6-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methanolYield 70%

Procedure

A mixture of crude (1R,2S,3R,5R)-3-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)cyclopentane-1,2-diol (10 g, ˜20 mmol, 54% pure by NMR) and 2,2-dimethoxypropane (100 mL, 800 mmol) was treated with p-toluenesulfonic acid monohydrate (7.28 g, 38.3 mmol) and the yellow-brown reaction mixture was stirred vigorously for 1.25 h, at which time the only solids were a fine tan precipitate; HPLC indicated nearly complete consumption of the starting material. The reaction mixture was diluted with water (30 mL) and neutralized with solid NaHCO3 (4.80 g, 57.1 mmol). The volatiles were carefully removed in vacuo and the resulting brown aqueous solution was extracted with EtOAc (3×100 mL). The combined organics were dried (Na2SO4) and concentrated in vacuo to afford a tan paste. Purification by column chromatography (4×22 cm silica; 0-66% EtOAc/Hex) afforded the title compound (4.38 g, 70%, one step) as a colorless foam/glass: MS (ESI+) for C15H18ClN3O3 m/z 324.2 (M+H)+; MS (ESI−) for C15H18ClN3O3 m/z 368.2 (M+HCO2)−; HPLC purity>95% (ret. time, 3.034 min).

Workup

  1. customconsumption of the starting material
  2. additionThe reaction mixture was diluted with water (30 mL)
  3. customThe volatiles were carefully removed in vacuo
  4. extractionthe resulting brown aqueous solution was extracted with EtOAc (3×100 mL)
  5. dry with materialThe combined organics were dried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customto afford a tan paste
  8. customPurification by column chromatography (4×22 cm silica; 0-66% EtOAc/Hex)

Sources & evidence

ORD record
ord-98194a257eda445991490c45b08d8ee2
Source dataset
uspto-grants-2016_07
Patent number
US09394310B2

Reaction notes

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