Hydrochloric Acid → 4-(5-carboxy-1-methylindol-3-ylmethyl)-3-methoxy-N-(2-methylphenylsulfonyl)benzamide

HRID 1198298Notes

Reaction equation

HRID 1198298 reaction equation
C[O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([CH3:14])[CH:9]=[C:8]2[CH2:15][C:16]1[CH:34]=[CH:33][C:19]([C:20]([NH:22][S:23]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[CH3:32])(=[O:25])=[O:24])=[O:21])=[CH:18][C:17]=1[O:35][CH3:36])=[O:4].[OH-].[Na+].O.Cl>C(OCCCC)(=O)C.O1CCCC1>[C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([CH3:14])[CH:9]=[C:8]2[CH2:15][C:16]1[CH:34]=[CH:33][C:19]([C:20]([NH:22][S:23]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[CH3:32])(=[O:25])=[O:24])=[O:21])=[CH:18][C:17]=1[O:35][CH3:36])([OH:4])=[O:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14798Sodium HydroxideHCID 151044784-(5-methoxycarbonyl-1-methylindol-3-ylmethyl)-3-methoxy-N-(2-methylphenylsulfonyl)benzamide

Product 1

HCID 151044754-(5-carboxy-1-methylindol-3-ylmethyl)-3-methoxy-N-(2-methylphenylsulfonyl)benzamide

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 31272Butyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of the product of step d) (15 g, 23.8 mmole), concentrated sodium hydroxide liquor (6.75 ml, 119 mmole), water (85 ml) and tetrahydrofuran (18 ml) was stirred for three hours at 65° C., and the now homogeneous solution cooled to 50°-55° C. and maintained at this temperature during the subsequent acidification and extraction. Concentrated hydrochloric acid was added to a pH of 7-8, followed by addition of tetrahydrofuran (44 ml) and n-butyl acetate (29 ml), and further adjustment of the pH to 1-2. The reaction mixture was allowed to settle and the lower aqueous layer separated. The organic layer was washed with 5% brine solution (2×20 ml). The tetrahydrofuran was removed by distillation (ca 40 ml distillate collected at a jacket temperature of 95° C.), and the residual mixture cooled to 15°-20° C. The product was collected by filtration, washed with butyl acetate (15 ml) and dried at 50° C. The yield of 4-(5-carboxy-1-methylindol-3-ylmethyl)-3-methoxy-N-(2-methylphenylsulfonyl)-benzamide was 11.08 g (94%); m.p. 264°-267° C.; NMR (250 MHz, DMSO-d6): 2.63 (s, 3H, ArCH3), 3.78 (s, 3H, NCH3), 3.95 (s, 3H, OCH3), 4.08 (s, 2H, ArCH2Ar'), 7.18 (d, 1H), 7.22 (s, 1H), 7.38-7.65 (m, 6H), 7.79 (d, 1H), 8.06 (d, 1H), 8.20 (s, 1H).

Workup

  1. temperaturethe now homogeneous solution cooled to 50°-55° C.
  2. temperaturemaintained at this temperature during the subsequent acidification and extraction
  3. customthe lower aqueous layer separated
  4. washThe organic layer was washed with 5% brine solution (2×20 ml)
  5. customThe tetrahydrofuran was removed by distillation (ca 40 ml
  6. distillationdistillate collected at a jacket temperature of 95° C.), and the residual mixture
  7. temperaturecooled to 15°-20° C
  8. filtrationThe product was collected by filtration
  9. washwashed with butyl acetate (15 ml)
  10. customdried at 50° C

Sources & evidence

ORD record
ord-6e67b50be03c46b7a067e0d16bdbd0ca
Source dataset
uspto-grants-1994_01
Patent number
US05280125

Reaction notes

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