Sodium Hydroxide → HCID 131734619, compound

HRID 596029Notes

Reaction equation

HRID 596029 reaction equation
[Si:1]([O:8][C@H:9]1[CH2:14][CH2:13][C@@:12]([C:20]2[CH:25]=[N:24][C:23]([N:26]3[C:30]([CH3:31])=[CH:29][CH:28]=[C:27]3[CH3:32])=[CH:22][N:21]=2)([C:15]([O:17]CC)=[O:16])[CH2:11][C@@H:10]1[F:33])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[OH-].[Na+]>C(O)C>[Si:1]([O:8][C@H:9]1[CH2:14][CH2:13][C:12]([C:20]2[CH:25]=[N:24][C:23]([N:26]3[C:30]([CH3:31])=[CH:29][CH:28]=[C:27]3[CH3:32])=[CH:22][N:21]=2)([C:15]([OH:17])=[O:16])[CH2:11][C@@H:10]1[F:33])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 131734620HCID 131734620, compound

Product 1

HCID 131734619HCID 131734619, compoundYield 153.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
30 °C

Procedure

To a 1 L flask was added (1R,3S,4S)-ethyl 4-((tert-butyldimethylsilyl)oxy)-1-(5-(2,5-dimethyl-1H-pyrrol-1-yl)pyrazin-2-yl)-3-fluorocyclohexanecarboxylate (48 g, 67 mmol), ethanol (250 mL) followed by 11% aqueous NaOH solution (112 g, 300 mmol). The reaction mixture was stirred at 30±5° C. for 16 hours, and then was quenched with 10% aqueous HCl (70 mL) to pH=6˜7. After distillation of ethanol under reduced pressure (50±5° C., 50˜100 mbar), the pH of the resulting mixture was adjusted to between 4 and 5 with 10% HCl. The aqueous solution was extracted twice with IPAc (200 mL×2). The combined organic layers were washed with 10% brine (200 mL) and concentrated under reduced pressure (50±5° C., 50˜100 mbar) to give 46 g of (1RS,3S,4S)-4-((tert-butyldimethylsilyl)oxy)-1-(5-(2,5-dimethyl-1H-pyrrol-1-yl)pyrazin-2-yl)-3-fluorocyclohexanecarboxylic acid which was used for next step without further purifications. HPLC retention time=7.390 min (Instrument: Agilent Technologies 1200 series. Column: Waters Xbridge C18, 150*3.0 mm, 3 um. Column temperature: 35° C. Flow rate: 0.70 mL/min. Detection: 210 nm/DAD. Mobile phase composition: A: 0.1% H3PO4 in water; B: acetonitrile. Gradient: 0 min: 90% A, 10% B; 5 min: 100% B; 11 min 100% B), LC-MS: [M+H]+=448.2415.

Workup

  1. customwas quenched with 10% aqueous HCl (70 mL) to pH=6˜7
  2. distillationAfter distillation of ethanol under reduced pressure (50±5° C., 50˜100 mbar)
  3. extractionThe aqueous solution was extracted twice with IPAc (200 mL×2)
  4. washThe combined organic layers were washed with 10% brine (200 mL)
  5. concentrationconcentrated under reduced pressure (50±5° C., 50˜100 mbar)

Sources & evidence

ORD record
ord-e4926ab693194ebbacf0debbb81ce9a7
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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