Indole-3-Acetic Acid → 1-(Benzyloxycarbonyl)indol-3-yl acetic Acid

HRID 1671641Notes

Reaction equation

HRID 1671641 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][C:11]([OH:13])=[O:12])=[CH:2]1.C(=O)=O.CC(C)=O.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Cl[C:32]([O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:33]>C1COCC1>[CH2:35]([O:34][C:32]([N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][C:11]([OH:13])=[O:12])=[CH:2]1)=[O:33])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Participants

6

Reactant 4

HCID 802Indole-3-Acetic AcidHCID 10387Benzyl chloroformateHCID 2733832Lithium HexamethyldisilazideHCID 18522661Acetone cardice

Product 1

HCID 108286661-(Benzyloxycarbonyl)indol-3-yl acetic AcidYield 98%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Indole-3-acetic acid (13 g, 74 mmol) was taken up in 130 mL anhydrous THF in a flame-dried, 2-necked 1 L round-bottomed flask, under an inert atmosphere, and cooled to −78° C. (dry ice/acetone bath). A 1.0 M THF solution of LHMDS (163 mL, 0.163 mol) was added via syringe over 30 minutes, and the reaction mixture allowed to stir for an additional 30 minutes at −78° C. once the addition was complete. Next, benzyl chloroformate (11.7 mL, 13.9 g, 81.6 mmol) was added dropwise via syringe. Stirring was then continued for 1 hour. To work up the reaction mixture, it was quenched with 2 M HCl, and partitioned between 2 M HCl and ethyl acetate. The aqueous layer was extracted with additional ethyl acetate, and the combined organic layers washed with brine, dried over anhydrous MgSO4, filtered, and evaporated to give a white solid with a pinkish tinge (22.49 g, 98% yield): 1H NMR (400 MHz, DMSO-d6) δ 3.71 (s, 2H) 5.47 (s, 2H) 7.27 (t, J=7.2 Hz, 1H) 7.32-7.47 (m, 4H) 7.54 (d, J=6.8 Hz, 2H) 7.58 (d, J=7.6 Hz, 1H) 7.68 (s, 1H) 8.08 (d, J=8.1 Hz, 1H) 12.43 (s, 1H); HRMS (ESI+) calcd for C18H16NO4 (MH+) 310.1074. found 310.1080.

Workup

  1. additionthe addition
  2. stirringStirring
  3. waitwas then continued for 1 hour
  4. customwas quenched with 2 M HCl
  5. custompartitioned between 2 M HCl and ethyl acetate
  6. extractionThe aqueous layer was extracted with additional ethyl acetate
  7. washthe combined organic layers washed with brine
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationfiltered
  10. customevaporated
  11. customto give a white solid with a pinkish tinge (22.49 g, 98% yield)

Sources & evidence

ORD record
ord-df0af76991aa4881bb48291dc9a58acb
Source dataset
uspto-grants-2011_08
Patent number
US07994333B2

Reaction notes

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