Hydrochloric Acid → HCID 11856120, compound

HRID 1666728Notes

Reaction equation

HRID 1666728 reaction equation
O.[OH-].[Li+].C([O:6][C:7](=[O:35])[CH2:8][N:9]1[C:17]2[C:12](=[CH:13][C:14]([F:18])=[CH:15][CH:16]=2)[C:11]([CH2:19][C:20]2[N:21]([S:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)(=[O:27])=[O:26])[CH:22]=[CH:23][CH:24]=2)=[C:10]1[CH3:34])C.Cl>O1CCCC1.O>[C:28]1([S:25]([N:21]2[CH:22]=[CH:23][CH:24]=[C:20]2[CH2:19][C:11]2[C:12]3[C:17](=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=3)[N:9]([CH2:8][C:7]([OH:35])=[O:6])[C:10]=2[CH3:34])(=[O:27])=[O:26])[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 67445232HCID 67445232, compound

Product 1

HCID 11856120HCID 11856120, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

Lithium hydroxide monohydrate (138 mg, 3.3 mmol) was added in one portion to a stirred solution of [3-(1-benzenesulfonyl-1H-pyrrol-2-ylmethyl)-5-fluoro-2-methyl-indol-1-yl]-acetic acid ethyl ester (507 mg, 1.1 mmol) in tetrahydrofuran:water (2:1; 10 ml) and the resulting mixture stirred at room temperature for 3 h. The solution was adjusted to pH 1 with 1M hydrochloric acid and then concentrated in vacuo to leave a yellow solid. The solid was partitioned between ethyl acetate (30 ml) and water (30 ml) and then the organic layer separated. The aqueous layer was extracted with ethyl acetate (2×20 ml) and the combined organic extracts were then dried and concentrated in vacuo to leave an off-white solid. Purification by flash column chromatography on silica gel eluting with 10% methanol:dichloromethane gave the carboxylic acid (130 mg, 28%) as a white solid, δH (250 MHz, d6-DMSO) 7.84 (2H, d J 7.1 Hz, Ar), 7.74 (1H, d J 7.1 Hz, Ar), 7.65-7.59 (2H, m, Ar), 7.44-7.41 (1H, m, Ar), 7.35-7.30 (1H, m, Ar), 6.82 (1H, td J 9.3, 2.4 Hz, Ar), 6.42 (1H, dd J 9.8, 2.4 Hz, Pyrrole-CH), 6.23-6.21 (1H, m, Pyrrole-CH), 5.56 (1H, br s, Pyrrole-CH), 4.94 (2H, s, CH2-Pyrrole), 4.02 (2H, s, CH2CO2H), 2.52 (3H, masked s, CCH3); Tr=1.63, m/z (ES+) (M+H)+ 427.19.

Workup

  1. concentrationconcentrated in vacuo
  2. customto leave a yellow solid
  3. customThe solid was partitioned between ethyl acetate (30 ml) and water (30 ml)
  4. customthe organic layer separated
  5. extractionThe aqueous layer was extracted with ethyl acetate (2×20 ml)
  6. customthe combined organic extracts were then dried
  7. concentrationconcentrated in vacuo
  8. customto leave an off-white solid
  9. customPurification by flash column chromatography on silica gel eluting with 10% methanol

Sources & evidence

ORD record
ord-2d16a9ddefb14803b27a28cf0991bcbd
Source dataset
uspto-grants-2011_10
Patent number
US08044088B2

Reaction notes

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