Sodium Hydroxide → HCID 86698711, compound

HRID 338368Notes

Reaction equation

HRID 338368 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 (1M, 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 1M 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, 1H), 11.96 (br. s, 1H), 8.10 (d, J=2.2 Hz, 1H), 7.98 (s, 1H), 7.65 (s, 1H), 7.29 (d, J=7.8 Hz, 1H), 7.05 (d, J=1.5 Hz, 1H), 6.99 (dd, J=7.6, 1.5 Hz, 1H), 5.89 (s, 1H), 5.02 (d, J=6.8 Hz, 2H), 4.67 (d, J=6.8 Hz, 2H), 3.81 (s, 3H)

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-011a7ee36efb418180bcfd75ca92f660
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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