Aluminium lithium hydride → HCID 44601273, compound

HRID 1177481Notes

Reaction equation

HRID 1177481 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[F:7][C:8]1[CH:9]=[C:10]([CH2:32][CH:33]([C:39](OCC)=[O:40])[C:34](OCC)=[O:35])[CH:11]=[CH:12][C:13]=1[C:14]1[S:15][C:16]2[C:21]([N:22]=1)=[CH:20][CH:19]=[C:18]([C:23]1([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH2:25][CH2:24]1)[N:17]=2>C1COCC1>[F:7][C:8]1[CH:9]=[C:10]([CH2:32][CH:33]([CH2:39][OH:40])[CH2:34][OH:35])[CH:11]=[CH:12][C:13]=1[C:14]1[S:15][C:16]2[C:21]([N:22]=1)=[CH:20][CH:19]=[C:18]([C:23]1([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH2:25][CH2:24]1)[N:17]=2

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 67112866HCID 67112866, compound

Product 1

HCID 44601273HCID 44601273, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a slurry of lithium aluminum hydride, 1.0 m solution in tetrahydrafuran (1.39 mL, 1.39 mmol) in 4 mL THF at 0° C. under nitrogen was added diethyl 2-((3-fluoro-4-(5-(1-phenyl-cyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)methyl)malonate (0.240 g, 0.463 mmol) as a solution in 4 mL THF slowly dropwise via syringe, with 1 mL THF rinse. The slightly yellow reaction mixture was allowed to stir 1 h, then the bath was removed. After 4 h at ambient temperature, the reaction was judged complete. Water (0.05 mL) was added carefully dropwise under nitrogen, followed by 0.10 mL 5 N NaOH, followed by 0.15 mL water. After 1 h, the reaction mixture was filtered to remove a solid, rinsing with THF, and concentrated in vacuo. The material was adsorbed onto 2 g silica gel from DCM/MeOH and purify by silica gel chromatography, 12 g, 20-100% EA/hexanes to give 2-((3-fluoro-4-(5-(1-phenylcyclopropyl)-thiazolo[5,4-b]pyridine-2-yl)phenyl)methyl)propane-1,3-diol as a light yellow solid. MS (ESI) m/z: calculated: 434.2; Observed: 435.1 (M++1).

Workup

  1. washwith 1 mL THF rinse
  2. customthe bath was removed
  3. waitAfter 4 h at ambient temperature
  4. additionWater (0.05 mL) was added carefully dropwise under nitrogen
  5. waitAfter 1 h
  6. filtrationthe reaction mixture was filtered
  7. customto remove a solid
  8. washrinsing with THF
  9. concentrationconcentrated in vacuo
  10. custompurify by silica gel chromatography, 12 g, 20-100% EA/hexanes

Sources & evidence

ORD record
ord-8e055dd1ecdb462594a838774edeb82c
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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