Diisobutylaluminum hydride → 1,1-Dimethylethyl 6-chloro-4-(hydroxymethyl)-1H-indole-1-carboxylate

HRID 1747471Notes

Reaction equation

HRID 1747471 reaction equation
C[O:2][C:3]([C:5]1[C:6]2[CH:7]=[CH:8][N:9]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C:10]=2[CH:11]=[C:12]([Cl:14])[CH:13]=1)=O.CC(C[AlH]CC(C)C)C>O1CCCC1>[C:18]([O:17][C:15]([N:9]1[C:10]2[C:6](=[C:5]([CH2:3][OH:2])[CH:13]=[C:12]([Cl:14])[CH:11]=2)[CH:7]=[CH:8]1)=[O:16])([CH3:21])([CH3:19])[CH3:20]

Participants

4

Reactant 2

HCID 14487Diisobutylaluminum hydride2×HCID 594976181-tert-Butyl 4-methyl 6-chloro-1H-indole-1,4-dicarboxylate

Product 1

HCID 594973521,1-Dimethylethyl 6-chloro-4-(hydroxymethyl)-1H-indole-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

6-Chloro-indole-1,4-dicarboxylic acid 1-tert-butyl ester 4-methyl ester 13.2 g (42 mmol) is dissolved in 200 mL of dry tetrahydrofuran and cooled to −78° C. The reaction is equipped with a dropping funnel and the reaction purged with nitrogen. DIBAL-H (85 mL, 1.5 M/L 128 mmol) is added via a syringe to the dropping funnel and the reagent added over the course of 10 minutes. The reaction is stirred for 30 minutes then tested via LC/MS for completion. An additional two equivalents of DIBAL-H is added to the reaction via syringe and the reaction stirred for an additional hour. After 1 hour, the reaction is quenched by the slow addition of 500 mL of saturated Rochelle's salt, and slowly warmed to room temperature with stirring overnight. The resulting biphasic mixture is separated and the water layer extracted with DCM. The combined organic layers were dried (MgSO4) filtered and evaporated in vacuo to give the title compound that is purified on silica gel with hexanes ethyl acetate as the eluent (9.5 g 34 mmol, 80%). LCMS (ESMS): m/z 282.9 (M+H+).

Workup

  1. customThe reaction is equipped with a dropping funnel
  2. customthe reaction purged with nitrogen
  3. additionthe reagent added over the course of 10 minutes
  4. stirringthe reaction stirred for an additional hour
  5. waitAfter 1 hour
  6. customthe reaction is quenched by the slow addition of 500 mL of saturated Rochelle's salt
  7. temperatureslowly warmed to room temperature
  8. stirringwith stirring overnight
  9. customThe resulting biphasic mixture is separated
  10. extractionthe water layer extracted with DCM
  11. dry with materialThe combined organic layers were dried (MgSO4)
  12. filtrationfiltered
  13. customevaporated in vacuo

Sources & evidence

ORD record
ord-f0969e05449e42179ed3105e12fe8ebc
Source dataset
uspto-grants-2015_10
Patent number
US09150556B2

Reaction notes

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