Hydrochloric Acid → Tert-butyl 4-(3-amino-6-(4-oxocyclohexyl)pyrazin-2-yl)-2-fluorobenzoate

HRID 595957Notes

Reaction equation

HRID 595957 reaction equation
[NH2:1][C:2]1[C:3]([C:18]2[CH:30]=[CH:29][C:21]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[C:20]([F:31])[CH:19]=2)=[N:4][C:5]([CH:8]2[CH2:17][CH2:16][C:11]3(OCC[O:12]3)[CH2:10][CH2:9]2)=[CH:6][N:7]=1.C(#N)C.Cl.[OH-].[Na+]>O>[NH2:1][C:2]1[C:3]([C:18]2[CH:30]=[CH:29][C:21]([C:22]([O:24][C:25]([CH3:27])([CH3:28])[CH3:26])=[O:23])=[C:20]([F:31])[CH:19]=2)=[N:4][C:5]([CH:8]2[CH2:17][CH2:16][C:11](=[O:12])[CH2:10][CH2:9]2)=[CH:6][N:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6342AcetonitrileHCID 14798Sodium HydroxideHCID 118045406Tert-butyl 4-(3-amino-6-(1,4-dioxaspiro[4.5]decan-8-yl)pyrazin-2-yl)-2-fluorobenzoate

Product 1

HCID 118045455Tert-butyl 4-(3-amino-6-(4-oxocyclohexyl)pyrazin-2-yl)-2-fluorobenzoateYield 93.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
25 °C

Procedure

To tert-butyl 4-(3-amino-6-(1,4-dioxaspiro[4.5]decan-8-yl)pyrazin-2-yl)-2-fluorobenzoate (14.34 g, 33.4 mmol) were added acetonitrile (250 mL), water (160 mL) and then 3 M aqueous solutionueous HCl (55.6 mL, 167 mmol). The reaction mixture was stirred at 25° C. for 30 min which was monitored by LCMS. The mixture was basified with 2 M NaOH aqueous solution under stirring to pH 9. Light yellow solid was precipitated out. Acetonitrile was removed under reduced pressure at room temperature. The solid was filtered and washed with water (2×30 mL), and dried under high vacuum overnight to afford tert-butyl 4-(3-amino-6-(4-oxocyclohexyl)pyrazin-2-yl)-2-fluorobenzoate (12 g, 31.1 mmol, 93%) as a light yellow solid. LCMS (m/z): 386.1 (MH+), 0.89 min; 1H NMR (400 MHz, ACETONITRILE-d3) δ ppm 8.05-7.89 (m, 2H) 7.73-7.51 (m, 2H), 5.14 (br. s., 2H), 3.30-3.08 (m, 1H), 2.64-2.48 (m, 2H), 2.40 (br. s., 2H), 2.30-2.17 (m, 2H), 2.12-1.99 (m, 2H), 1.96 (dt, J=4.99, 2.40 Hz, 4H), 1.61 (s, 9H).

Workup

  1. stirringunder stirring to pH 9
  2. customLight yellow solid was precipitated out
  3. customAcetonitrile was removed under reduced pressure at room temperature
  4. filtrationThe solid was filtered
  5. washwashed with water (2×30 mL)
  6. customdried under high vacuum overnight

Sources & evidence

ORD record
ord-248462f365e04722af0867576bcda43b
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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