Sodium Hydroxide → HCID 86698711, compound

HRID 1054711Notes

Reaction equation

HRID 1054711 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([O:13]C)=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:15]1[CH:20]=[CH:19][C:18]([C:21]2([OH:25])[CH2:24][O:23][CH2:22]2)=[C:17]([O:26][CH3:27])[CH:16]=1.[OH-].[Na+]>CO>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:13])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:15]1[CH:20]=[CH:19][C:18]([C:21]2([OH:25])[CH2:24][O:23][CH2:22]2)=[C:17]([O:26][CH3:27])[CH:16]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 86698709HCID 86698709, compound

Product 1

HCID 86698711HCID 86698711, compoundYield 17.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

To a mixture of methyl 6-chloro-5-[4-(3-hydroxyoxetan-3-yl)-3-methoxyphenyl]-1H-indole-3-carboxylate (100 mg, 0.258 mmol) in methanol (3 mL) and sodium hydroxide (1 M, 1.0 mL, 1.0 mmol) was heated to 70° C. for 24 hours. The reaction was concentrated under reduced pressure and the reaction was acidified with 1 M hydrochloric acid aqueous to pH=2 then diluted with ethyl acetate. The layers were separated and the aqueous extracted with ethyl acetate two additional times. The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure yielding 83 mg of the crude desired product. A portion of the crude material (60 mg) was purified by prep-HPLC (Phenomenex HILIC (Diol) 250×21.2 mm 5 μm; Mobile phase A: heptane; Mobile Phase B: Ethanol, gradient 95% A/5% B hold for 1.5 minutes, linear gradient to 0% A/100% B in 8.5 minutes, Hold at 0% A/100% B for 1 minutes; flow rate: 28 ml/min) to afford the title compound (16.9 mg, 17.5%) as a solid. MS (ES−) 372.0 (M−H)−. 1H NMR (500 MHz, DMSO-d6) δ 12.13 (br. s, 1 H), 11.96 (br. s, 1 H), 8.10 (d, J=2.2 Hz, 1 H), 7.98 (s, 1 H), 7.65 (s, 1 H), 7.29 (d, J=7.8 Hz, 1 H), 7.05 (d, J=1.5 Hz, 1 H), 6.99 (dd, J=7.6, 1.5 Hz, 1 H), 5.89 (s, 1 H), 5.02 (d, J=6.8 Hz, 2 H), 4.67 (d, J=6.8 Hz, 2 H), 3.81 (s, 3 H)

Workup

  1. concentrationThe reaction was concentrated under reduced pressure
  2. additionthen diluted with ethyl acetate
  3. customThe layers were separated
  4. extractionthe aqueous extracted with ethyl acetate two additional times
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customyielding 83 mg of the crude desired product
  9. customA portion of the crude material (60 mg) was purified by prep-HPLC (Phenomenex HILIC (Diol) 250×21.2 mm 5 μm; Mobile phase A: heptane; Mobile Phase B: Ethanol, gradient 95% A/5% B hold for 1.5 minutes, linear gradient to 0% A/100% B in 8.5 minutes, Hold at 0% A/100% B for 1 minutes; flow rate: 28 ml/min)

Sources & evidence

ORD record
ord-28e6003a404c40e7862671366a24ea18
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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