Triisopropyl borate → 5-Acetyl-2-methyl-indole-1-carboxylic acid tert-butyl ester

HRID 2078697Notes

Reaction equation

HRID 2078697 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17]3([CH3:22])[O:21]CCO3)=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].B(OC(C)C)(OC(C)C)O[CH:25](C)C.[Li+].CC([N-]C(C)C)C>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17](=[O:21])[CH3:22])=[CH:14][CH:15]=2)[CH:10]=[C:9]1[CH3:25])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 21531Triisopropyl borateHCID 2724682Lithium diisopropylamideHCID 576373041h-Indole-1-carboxylic acid,5-(2-methyl-1,3-dioxolan-2-yl)-,1,1-dimethylethyl ester2×

Product 1

HCID 670982245-Acetyl-2-methyl-indole-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 5-(2-methyl-[1,3]dioxolan-2-yl)-indole-1-carboxylic acid tert-butyl ester [4.96 g, 16.35 mmol, Intermediate (19)] in anhydrous tetrahydrofuran (20 mL) is added triisopropyl borate (4.61 g, 24.51 mmol) and cooled to 0° C. under N2. To it is added LDA (1.8M in heptane/tetrahydrofuran/ethylbenzene, 14 mL) drop wise at 0° C. over 40 minutes periods. After another 35 minutes, the reaction is quenched by the addition of aqueous 2N hydrochloric acid at 0° C. The white solid precipitated is slowly acidified with 3N hydrochloric acid till pH=3. The mixture became solution which is extracted twice with ethyl acetate (100 mL). The combined ethyl acetate phases are dried over sodium sulfate and filtered. The solid crude is triturated with acetonitrile and water to obtain 5-acetyl-2-methyl-indole-1-carboxylic acid tert-butyl ester (4.76 g, 96%, Intermediate (20)] as light yellow solid; 1H NMR (CDCl3): δ 8.30 (2.67, 3H), 8.18 (1H, d), 7.90 (1H, d), 6.78 (1H, s), 2.61 (3H, s), 1.62 (9H, s); LC/MS: ESI+ 304 (M+H)

Workup

  1. customthe reaction is quenched by the addition of aqueous 2N hydrochloric acid at 0° C
  2. customThe white solid precipitated
  3. extractionis extracted twice with ethyl acetate (100 mL)
  4. dry with materialThe combined ethyl acetate phases are dried over sodium sulfate
  5. filtrationfiltered
  6. customThe solid crude is triturated with acetonitrile and water

Sources & evidence

ORD record
ord-930668cf434744db834ccab3517c6eed
Source dataset
uspto-grants-2011_04
Patent number
US07928231B2

Reaction notes

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