Acetaldehyde → 1H-Indolamine

HRID 966509Notes

Reaction equation

HRID 966509 reaction equation
Cl.C(OC([C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18](OC3CCNC3)[CH:19]=2)[NH:14][C:13]=1C)=O)C1C=CC=CC=1.C(=O)C.C([BH3-])#[N:32].[Na+]>CO>[NH:14]1[C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:12]=[C:13]1[NH2:32]

Participants

5

Reactant 3

HCID 177AcetaldehydeHCID 5003444Sodium cyanoborohydrideHCID 1317251792-Methyl-5-(pyrrolidin-3-yloxy)-1h-indole-3-carboxylic acid benzyl ester, hydrochloride

Product 1

HCID 1220741H-IndolamineYield 31.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Crude 2-methyl-5-(pyrrolidin-3-yloxy)-1H-indole-3-carboxylic acid benzyl ester, hydrochloride (0.075 g, 0.194 mmol, 1 eq) was suspended in methanol (5 mL). Acetaldehyde (0.028 mL, 0.5 mmol, 2.6 eq) was added followed by the addition of sodium cyanoborohydride (0.032 g, 0.5 mmol, 2.6 eq). The reaction mixture was kept at pH 6 and stirred at room temperature. After 24 hours, the reaction was quenched with aqueous sodium bicarbonate, extracted several times with CH2Cl2. The combined organic layers were dried over sodium sulfate, loaded on silica gel and chromatographed (ethyl acetate/methanol/triethylamine 87/10/3). Impure product was further purified by reverse-phase prep-HPLC 10-100% Acetonitrile/water, 0.1% TFA. 0.008 g (10% yield) of the indole-amine was obtained as a brown semisolid: LC/MS (ESI+) 379 (M+1), Anal. (C23H26N2O3.TFA.1.0H2O) C, H, N.

Workup

  1. customthe reaction was quenched with aqueous sodium bicarbonate
  2. extractionextracted several times with CH2Cl2
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. customchromatographed (ethyl acetate/methanol/triethylamine 87/10/3)
  5. customImpure product was further purified by reverse-phase prep-HPLC 10-100% Acetonitrile/water, 0.1% TFA

Sources & evidence

ORD record
ord-c0d7956c025640109af80254f06aa67b
Source dataset
uspto-grants-2005_10
Patent number
US06951848B2

Reaction notes

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