Benzyl Chloride → 1-Phenyl-3-(phenylmethoxy)-1H-indole-2-carboxylic acid methyl ester

HRID 653145

Reaction equation

HRID 653145 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]([C:7]1[N:8]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:9]2[C:14]([C:15]=1[OH:16])=[CH:13][CH:12]=[CH:11][CH:10]=2)=[O:6].[CH2:23](Cl)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>CN(C)P(N(C)C)(N(C)C)=O>[CH3:3][O:4][C:5]([C:7]1[N:8]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:9]2[C:14]([C:15]=1[O:16][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[CH:13][CH:12]=[CH:11][CH:10]=2)=[O:6]

Participants

5

Reactant 3

HCID 7503Benzyl ChlorideHCID 24758Sodium hydrideHCID 54687160Methyl 3-hydroxy-1-phenyl-1H-indole-2-carboxylate

Product 1

HCID 138858261-Phenyl-3-(phenylmethoxy)-1H-indole-2-carboxylic acid methyl esterYield 54%

Reagents, catalysts & solvents 1

HCID 12679HexamethylphosphoramideSolvent2×

Procedure

A mixture of 1.2 g (0.025 mole) of 50% sodium hydride/mineral oil suspension in 20 ml of hexamethylphosphoramide under a nitrogen atmosphere was cooled in ice and treated over 15 minutes with a solution of 5.3 g (0.020 mole) of 3-hydroxy-1-phenyl-1H-indole-2-carboxlic acid methyl ester [P. Friedlander and K. Kurz, Chem. Ber., 55, 1597 (1922)] in 25 ml of hexamethylphosphoramide. The mixture was stirred in ice an additional one hour, 2.6 ml (2.9 g, 0.023 mole) of benzyl chloride was added in one portion, the ice bath was removed and stirring was continued for a total of 18 hours. The reaction mixture was added to 200 g of ice/water, stirred for one hour, and the precipitated product was filtered and washed with water. Recrystallization from aqueous methanol yielded 3.8 g (54% yield) of the ester product. An additional recrystallization as above yielded analytically pure ester, mp 117°-119° C.

Workup

  1. temperaturewas cooled in ice
  2. customthe ice bath was removed
  3. stirringstirring
  4. customwas continued for a total of 18 hours
  5. additionThe reaction mixture was added to 200 g of ice/water
  6. stirringstirred for one hour
  7. filtrationthe precipitated product was filtered
  8. washwashed with water
  9. customRecrystallization from aqueous methanol

Sources & evidence

ORD record
ord-bcc7c97dd21844328ed5cb7d5875aa91
Source dataset
uspto-grants-1987_06
Patent number
US04675332

Linked notes

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