Benzyl Alcohol → Benzyl 1H-indole-5-carboxylate

HRID 1975415Notes

Reaction equation

HRID 1975415 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]([OH:12])=[O:11])=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[CH2:13](O)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]([O:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[O:11])=[CH:7][CH:8]=2)[CH:3]=[CH:2]1

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 11776TriphenylphosphineHCID 742801H-Indole-5-Carboxylic AcidHCID 220568ethyl N-ethoxycarbonyliminocarbamate

Product 1

HCID 10264164Benzyl 1H-indole-5-carboxylateYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of indole-5-carboxylic acid (68.3 g), benzyl alcohol (64.9 g) and triphenylphosphine (157.0 g) in tetrahydrofuran (1.2 L) was cooled to 5° C. and treated dropwise with diethyl azodicarboxylate (90.0 g). Upon completion of the addition, the mixture was allowed to warm to room temperature. The reaction was stirred for 24 hours and then evaporated. The residue was taken up in diethyl ether (1 L) and filtered. The filtrate was evaporated to give a yellow syrup which was purified by flash chromatography, eluting sequentially with 2:1, 1:1 and 1:2 hexane:methylene chloride, to afford a yellow-white solid. This material was triturated with 1:1 hexane: methylene chloride (300 mL) and filtered to give benzyl indole-5-carboxylate as a white solid (74.2 g, 70%); mp 127°-129° C.; partial NMR (300 MHz, CDCl3): 5.39 (s, 2H, CH2), 6.61 (m, 1H, indole-H(2)), 8.56 (br, 1H, NH).

Workup

  1. additionUpon completion of the addition
  2. customevaporated
  3. filtrationfiltered
  4. customThe filtrate was evaporated
  5. customto give a yellow syrup which
  6. customwas purified by flash chromatography
  7. washeluting sequentially with 2:1, 1:1 and 1:2 hexane
  8. custommethylene chloride, to afford a yellow-white solid
  9. customThis material was triturated with 1:1 hexane
  10. filtrationmethylene chloride (300 mL) and filtered

Sources & evidence

ORD record
ord-6e094b6405c14bc890a5d835a5c30d97
Source dataset
uspto-grants-1994_02
Patent number
US05286740

Reaction notes

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