Diisobutylaluminumhydride → 2-[4-Chloro-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-2-yl]ethanol

HRID 928614Notes

Reaction equation

HRID 928614 reaction equation
[Cl:1][C:2]1[C:3]2[C:16]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)=[CH:15][S:14][C:4]=2[N:5]=[C:6]([CH2:8][C:9](OCC)=[O:10])[N:7]=1.[H-].C([Al+]CC(C)C)C(C)C>C1COCC1>[Cl:1][C:2]1[C:3]2[C:16]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)=[CH:15][S:14][C:4]=2[N:5]=[C:6]([CH2:8][CH2:9][OH:10])[N:7]=1

Participants

4

Reactant 2

HCID 21225700DiisobutylaluminumhydrideHCID 87518468Ethyl 2-[4-chloro-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-2-yl]acetate

Product 1

HCID 895796712-[4-Chloro-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-2-yl]ethanolYield 4.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Ethyl 2-[4-chloro-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-2-yl]acetate (9.98 g, 0.285 mol) was dissolved in dry THF (100 mL) under nitrogen. To this was added diisobutyl aluminium hydride (1 M in THF, 95 mL). The reaction was stirred at room temperature for 5.5 hrs before being quenched by careful addition to a saturated solution of Rochelle's salt. The mixture was stirred for 1 hr then allowed to stand overnight. The mixture was extracted with DCM (3×700 mL), the extracts were then combined, dried and concentrated in vacuo. The residue was purified by silica column chromatography eluting with DCM, then 3:1 v/v DCM/ethyl Acetate. Fractions were analysed by TLC, combined and concentrated to give 2-[4-chloro-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-2-yl]ethanol as a brown solid (4 g). LCMS RT=4.25 min, M+1=309.

Workup

  1. custombefore being quenched by careful addition to a saturated solution of Rochelle's salt
  2. stirringThe mixture was stirred for 1 hr
  3. waitto stand overnight
  4. extractionThe mixture was extracted with DCM (3×700 mL)
  5. customdried
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica column chromatography
  8. washeluting with DCM
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-333eb8f0c12e4f69b6758758e8f4f27f
Source dataset
uspto-grants-2016_03
Patent number
US09290511B2

Reaction notes

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