Potassium Carbonate → HCID 19065954, compound

HRID 481339Notes

Reaction equation

HRID 481339 reaction equation
[CH3:1][N:2]([CH3:7])[C:3](=O)[CH2:4][Cl:5].C[O:9][C:10]([C:12]1[N:13]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[C:14]2[C:19]([C:20]=1[OH:21])=[CH:18][C:17]([Cl:22])=[CH:16][CH:15]=2)=O.C(=O)([O-])[O-].[K+].[K+]>ClC1C=C2C(=CC=1)N(C1C=CC(F)=CC=1)C=C2SCCN(C)CCN1CCNC1=O>[ClH:5].[CH3:1][N:2]([CH2:3][CH2:4][O:21][C:20]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([Cl:22])[CH:18]=2)[N:13]([C:23]2[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=2)[C:12]=1[CH2:10][OH:9])[CH3:7]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 758862-chloro-N,N-dimethylacetamideHCID 54731653HCID 54731653, compound

Product 1

HCID 19065954HCID 19065954, compound

Reagents, catalysts & solvents 1

HCID 10647075HCID 10647075, compoundSolvent2×

Procedure

A solution of N,N-dimethyl-2-chloroacetamide (28 g) in acetone (300 mL) was added dropwise during 1 hour to a mixture of 5-chloro-1-(4-fluorophenyl)-3-hydroxy-1H-indole-2-carboxylic acid methyl ester (64 g) (prepared according to the method of Unangst et al. J.Heterocyc.Chem. 1984, 21, 709-714 and 1987, 24, 811-815) and potassium carbonate (40 g) in acetone (500 mL) kept at reflux. The mixture was refluxed for another 3 hours and subsequently worked-up. The resulting crude acetamide derivative crystallized from cyclohexane. Yield 72 g. Mp: 124°-125° C. To a suspension of LiAlH4 pellets (10 g) in dry THF (200 mL) kept at gentle reflux was added dropwise a solution of the acetamide derivative (35 g) in dry THF (300 mL). After reflux for 2 hours the mixture was cooled on an ice bath and excess LiAlH4 was hydrolyzed by cautiously adding a mixture of 10% water in THF. Inorganic salts were filtered off and the solvent evaporated in vacuo leaving the title compound as a visceous oil. Yield: 19 g. The hydrochloric acid salt of the title compound 9 crystallized from acetone by addition of a solution of hydrogenchloride gas in diethyl ether.mp 185°-186° C.; 1H NMR (DMSO-d6) δ 2.90 (s, 6H), 3.60 (t, 2H), 4.40 (s, 2H), 4.45 (t, 2H), 7.05 (d, 1H), 7.10 (dd, 1H), 7.40 (t, 2H), 7.55 (dd, 2H), 7.85 (d, 1H). MS (m/z) 363 (MH+), 72 (100); Anal (C19H20ClFN2O2.HCl) C, H, N.

Workup

  1. customprepared
  2. temperatureat reflux
  3. temperatureThe mixture was refluxed for another 3 hours
  4. customThe resulting crude acetamide derivative crystallized from cyclohexane
  5. additionTo a suspension of LiAlH4 pellets (10 g) in dry THF (200 mL)
  6. temperatureat gentle reflux
  7. additionwas added dropwise a solution of the acetamide derivative (35 g) in dry THF (300 mL)
  8. temperatureAfter reflux for 2 hours the mixture
  9. temperaturewas cooled on an ice bath
  10. additionby cautiously adding
  11. additiona mixture of 10% water in THF
  12. filtrationInorganic salts were filtered off
  13. customthe solvent evaporated in vacuo

Sources & evidence

ORD record
ord-acd96209c19942cb8ace1329463d5bd7
Source dataset
uspto-grants-1998_08
Patent number
US05789404

Reaction notes

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