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 2040636Notes

Reaction equation

HRID 2040636 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-50847aeddb704e7a83e5d3a5c719d1c9
Source dataset
uspto-grants-2013_11
Patent number
US08580762B2

Reaction notes

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