Hydrochloric Acid → HCID 86615555, compound

HRID 605191Notes

Reaction equation

HRID 605191 reaction equation
C1C2C(COC(=O)[NH:17][C:18]3[CH:23]=[CH:22][C:21]([S:24][C:25]4[CH:30]=[CH:29][C:28]([C:31](=[O:42])[NH:32][C:33]5[S:34][C:35]([C:38]([CH3:41])([CH3:40])[CH3:39])=[CH:36][N:37]=5)=[CH:27][C:26]=4[NH:43][C:44]4[C:45]5[CH:53]=[CH:52][C:51]([CH:54]([CH3:56])[CH3:55])=[N:50][C:46]=5[N:47]=[CH:48][N:49]=4)=[CH:20][CH:19]=3)C3C(=CC=CC=3)C=2C=CC=1.O.[OH-].[Li+].Cl>O1CCOCC1.O.C(OCC)(=O)C>[NH2:17][C:18]1[CH:23]=[CH:22][C:21]([S:24][C:25]2[CH:30]=[CH:29][C:28]([C:31]([NH:32][C:33]3[S:34][C:35]([C:38]([CH3:39])([CH3:40])[CH3:41])=[CH:36][N:37]=3)=[O:42])=[CH:27][C:26]=2[NH:43][C:44]2[C:45]3[CH:53]=[CH:52][C:51]([CH:54]([CH3:56])[CH3:55])=[N:50][C:46]=3[N:47]=[CH:48][N:49]=2)=[CH:20][CH:19]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 86615556HCID 86615556, compound

Product 1

HCID 86615555HCID 86615555, compoundYield 65.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
65 °C

Procedure

A solution of the product of Example 161E (123.4 mg, 0.1558 mmol) in 1,4-dioxane (4 mL) was treated with a solution of lithium hydroxide monohydrate (13 mg, 0.3 116 mmol) in water (2 mL) at ambient temperature, then heated at 65° C. for 1 hour. The reaction was cooled to room temperature, diluted with ethyl acetate (100 mL) and water (30 mL), adjusted the aqueous pH to 6 with 1N aqueous hydrochloric acid, and separated the layers. The organic phase was washed with water (2×25 mL) and brine (25 mL), dried over anhydrous sodium sulfate, filtered, and concentrated by rotary evaporation in vacuo. Purification of the residue by silica gel flash chromatography with 4% methanol/methylene chloride afforded the title compound (58 mg, 65%). 1H NMR (300 MHz, DMSO-d6) δ ppm: 1.28 (s, 9 H) 1.34 (d, J=6.99 Hz, 6 H) 3.17-3.34 (m, 1 H) 5.64 (s, 2 H) 6.65 (d, J=8.46 Hz, 2 H) 6.80 (s, 1 H) 6.82 (d, J=8.46 Hz, 1 H) 7.16 (d, J=8.46 Hz, 2 H) 7.65 (d, J=8.46 Hz, 1 H) 7.88-7.98 (dd, 1 H) 8.11 (s, 1 H) 8.58 (s, 1 H) 8.89 (d, J=8.46 Hz, 1 H) 10.13 (s, 1 H) 12.47 (s, 1 H); MS (ESI+) m/z 570 (M+H)+, (ESI−) m/z 568 (M−H)−.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customseparated the layers
  3. washThe organic phase was washed with water (2×25 mL) and brine (25 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated by rotary evaporation in vacuo
  7. customPurification of the residue by silica gel flash chromatography with 4% methanol/methylene chloride

Sources & evidence

ORD record
ord-eb0fa1a3ca7645baa99bf7c4f75b2d99
Source dataset
uspto-grants-2011_03
Patent number
US07910595B2

Reaction notes

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