2,2-Dimethoxypropane → {(3aR,4R,6R,6aS)-6-[(6-Chloropyrimidin-4-yl)amino}-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]methanol

HRID 1397512Notes

Reaction equation

HRID 1397512 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C@@H:9]2[CH2:13][C@H:12]([CH2:14][OH:15])[C@@H:11]([OH:16])[C@H:10]2[OH:17])[CH:3]=1.O.[C:19]1(C)[CH:24]=CC(S(O)(=O)=O)=C[CH:20]=1.COC(OC)(C)C>CO>[Cl:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C@H:9]2[C@@H:10]3[O:17][C:19]([CH3:24])([CH3:20])[O:16][C@@H:11]3[C@@H:12]([CH2:14][OH:15])[CH2:13]2)[CH:3]=1

Participants

5

Reactant 3

HCID 64952,2-DimethoxypropaneHCID 521998p-Toluenesulfonic acid monohydrateHCID 59671293(1R,2S,3R,5R)-3-[(6-chloropyrimidin-4-yl)amino]-5-(hydroxymethyl)cyclopentane-1,2-diol

Product 1

HCID 59671267{(3aR,4R,6R,6aS)-6-[(6-Chloropyrimidin-4-yl)amino}-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]methanolYield 45.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of (1R,2S,3R,5R)-3-[(6-chloropyrimidin-4-yl)amino]-5-(hydroxymethyl)cyclopentane-1,2-diol (255 mg, 0.982 mmol), p-toluenesulfonic acid monohydrate (187 mg, 0.982 mmol) and 2,2-dimethoxypropane (0.670 mL, 0.545 mmol) in MeOH (5.00 mL) was stirred overnight. The reaction was quenched via addition of saturated aqueous NaHCO3 solution (10 mL) and MeOH was removed in vacuo. The aqueous mixture was extracted with DCM (4×20 mL) and the combined organics were concentrated in vacuo. The crude mixture was purified via silica gel chromatography eluting with a gradient of 0 to 10% MeOH in DCM to afford the title compound (135 mg, 45.8%). LC/MS: Rt=1.77 min, ES+ 300. (AA standard).

Workup

  1. customThe reaction was quenched via addition of saturated aqueous NaHCO3 solution (10 mL) and MeOH
  2. customwas removed in vacuo
  3. extractionThe aqueous mixture was extracted with DCM (4×20 mL)
  4. concentrationthe combined organics were concentrated in vacuo
  5. customThe crude mixture was purified via silica gel chromatography
  6. washeluting with a gradient of 0 to 10% MeOH in DCM

Sources & evidence

ORD record
ord-165273c934954bbfbbe40da20a1dc8b0
Source dataset
uspto-grants-2014_12
Patent number
US08901136B2

Reaction notes

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