Aluminium lithium hydride → tert-Butyl 3-(2-(5-fluoro-2-hydroxyphenyl)quinazolin-4-ylamino)-trans-4-(hydroxymethyl)pyrrolidine-1-carboxylate

HRID 2189234Notes

Reaction equation

HRID 2189234 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([OH:36])=[C:6]([C:8]2[NH:17][CH:16]([NH:18][C@@H:19]3[CH2:23][N:22]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:21][C@H:20]3[C:31](OCC)=[O:32])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9]=2)[CH:7]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([OH:36])=[C:6]([C:8]2[N:17]=[C:16]([NH:18][C@H:19]3[C@H:20]([CH2:31][OH:32])[CH2:21][N:22]([C:24]([O:26][C:27]([CH3:29])([CH3:28])[CH3:30])=[O:25])[CH2:23]3)[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9]=2)[CH:7]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 178472532trans-1-Tert-butyl 3-ethyl 4-(2-(5-fluoro-2-hydroxyphenyl)-3,4-dihydroquinazolin-4-ylamino)pyrrolidine-1,3-dicarboxylate

Product 1

HCID 137252534tert-Butyl 3-(2-(5-fluoro-2-hydroxyphenyl)quinazolin-4-ylamino)-trans-4-(hydroxymethyl)pyrrolidine-1-carboxylateYield 30.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

trans-1-tert-Butyl 3-ethyl 4-(2-(5-fluoro-2-hydroxyphenyl)-3,4-dihydroquinazolin-4-ylamino)pyrrolidine-1,3-dicarboxylate (0.093 g, 0.19 mmol, synthesised using methods outlined in Synthesis 84) was dissolved in THF (1.8 mL) and cooled to 0° C. A 1 M solution of LiAlH4 in THF (0.375 mL, 0.38 mmol) was added dropwise and the mixture was stirred at this temperature for 15 min. The reaction was quenched with sodium potassium tartrate (2 drops) and diluted with water (10 mL). The mixture was extracted with dichloromethane (3×50 mL) and the combined organic extracts were dried (MgSO4) and concentrated in vacuo. The residue was purified by silica column chromatography eluting with 25% ethyl acetate in hexane to give the title compound as a yellow solid (0.026 g, 30%).

Workup

  1. customThe reaction was quenched with sodium potassium tartrate (2 drops)
  2. additiondiluted with water (10 mL)
  3. extractionThe mixture was extracted with dichloromethane (3×50 mL)
  4. dry with materialthe combined organic extracts were dried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica column chromatography
  7. washeluting with 25% ethyl acetate in hexane

Sources & evidence

ORD record
ord-e6fd116c3e144169a2ec1edfc8dc0456
Source dataset
uspto-grants-2012_12
Patent number
US08324226B2

Reaction notes

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