Aluminium lithium hydride → HCID 58201773, compound

HRID 1847604Notes

Reaction equation

HRID 1847604 reaction equation
[CH3:1][C:2]1([CH3:34])[O:6][C@@H:5]([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][C:13]([N+:18]([O-:20])=[O:19])=[C:14]([F:17])[CH:15]=3)[CH:10]=[C:9]2[C:21]([CH3:33])([CH3:32])[C:22](OCC2C=CC=CC=2)=[O:23])[CH2:4][O:3]1.CC1(C)O[C@@H](CN2C3C(=CC([N+]([O-])=O)=C(F)C=3)C=C2C(C)(C)C(OC[C@H]2COC(C)(C)O2)=O)CO1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[CH3:1][C:2]1([CH3:34])[O:6][C@@H:5]([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][C:13]([N+:18]([O-:20])=[O:19])=[C:14]([F:17])[CH:15]=3)[CH:10]=[C:9]2[C:21]([CH3:33])([CH3:32])[CH2:22][OH:23])[CH2:4][O:3]1

Participants

5

Reactant 3

HCID 21226445Aluminium lithium hydrideHCID 58201793HCID 58201793, compoundHCID 58201808HCID 58201808, compound

Product 1

HCID 58201773HCID 58201773, compoundYield 49%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The mixture of crude reaction mixture of (S)-benzyl 2-(1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-5-nitro-1H-indol-2-yl)-2-methylpropanoate and ((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl 2-(1-(((S)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-5-nitro-1H-indol-2-yl)-2-methylpropanoate was dissolved in THF (15 mL) and cooled in an ice-water bath. LiAlH4 (2.8 mL of 1 M solution, 2.8 mmol) was added dropwise. After addition was complete the reaction was stirred for 5 minutes. The reaction was quenched by adding water (0.5 mL), 15% NaOH solution (0.5 mL) and then water (1.5 mL). The mixture was filtered over Celite, and the solids were washed with THF and ethyl acetate. The filtrate was concentrated and purified by column chromatography (30-60% ethyl acetate-hexanes) to obtain the product as a brown oil (505 mg, 49% over 2 steps). ESI-MS m/z calc. 366.4, found 367.3 (M+1)+. Retention time 1.68 minutes. 1H NMR (400 MHz, DMSO-d6) δ 8.34 (d, J=7.6 Hz; 1H), 7.65 (d, J=13.5 Hz, 1H), 6.57 (s, 1H), 4.94 (t, J=5.4 Hz, 1H), 4.64-4.60 (m, 1H), 4.52-4.42 (m, 2H), 4.14 (dd, J=6.2, 8.4 Hz, 1H), 3.74 (dd, J=7.0, 8.3 Hz, 1H), 3.63-3.53 (m, 2H), 1.42 (s, 3H), 1.37 (m, 6H) and 1.19 (s, 3H) ppm.

Workup

  1. additionThe mixture of crude
  2. temperaturecooled in an ice-water bath
  3. additionAfter addition
  4. customThe reaction was quenched
  5. additionby adding water (0.5 mL), 15% NaOH solution (0.5 mL)
  6. filtrationThe mixture was filtered over Celite
  7. washthe solids were washed with THF and ethyl acetate
  8. concentrationThe filtrate was concentrated
  9. custompurified by column chromatography (30-60% ethyl acetate-hexanes)

Sources & evidence

ORD record
ord-6982644ee0814733833bbc5fee5f6420
Source dataset
uspto-grants-2015_02
Patent number
US08952050B2

Reaction notes

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