Hydrochloric Acid → HCID 118077991, compound

HRID 1482779Notes

Reaction equation

HRID 1482779 reaction equation
[I:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)[C:3]=1[C@@H:21]([CH2:23][C:24]([O:26]C)=[O:25])[CH3:22].O.[OH-].[Li+].Cl>O1CCCC1.O>[C:17]([O:16][C:14]([N:11]1[CH2:10][CH2:9][N:8]([C:4]2[C:3]([C@H:21]([CH3:22])[CH2:23][C:24]([OH:26])=[O:25])=[C:2]([I:1])[N:7]=[CH:6][N:5]=2)[CH2:13][CH2:12]1)=[O:15])([CH3:20])([CH3:18])[CH3:19]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 118078118HCID 118078118, compound

Product 1

HCID 118077991HCID 118077991, compoundYield 92.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

Into a solution of (R)-tert-butyl 4-(6-iodo-5-(4-methoxy-4-oxobutan-2-yl)pyrimidin-4-yl)piperazine-1-carboxylate (219 g, 0.447 mol) in tetrahydrofuran (657 mL) was added a solution of lithium hydroxide monohydrate (56.2 g, 1.34 mol) in 329 mL of water at 25° C. The mixture was stirred at 25° C. for 5 h. The bottom aqueous layer was discarded. The mixture was acidified with 1 N hydrochloric acid at 5° C. to give a final pH value of between about 1 to 2. The layers were separated. The top layer was then extracted with isopropyl acetate (440 mL×3), combined with the bottom layer, and washed with water (220 mL×2). The solvents was distilled off at reduced pressure below 50° C. The residual isopropyl acetate was azeotroped off with heptane under reduced pressure below 50° C. Product gradually precipitated out and was filtered to give an off-white to light yellow powder (196 g, 84% yield). 1H NMR (300 MHz, CDCl3) δ 8.27 (s, 1H), 3.80-3.68 (m, 1H), 3.59-3.56 (m, 4H), 3.23-3.14 (m, 5H), 2.86 (dd, J=16.5, 5.4 Hz, 1H), 1.50 (d, J=7.2 Hz, 3H), 1.48 (s, 9H). HRMS calcd. For C17H26IN4O4 [M+H]+: 477.0993. found 477.0995.

Workup

  1. customto give a final pH value of between about 1 to 2
  2. customThe layers were separated
  3. extractionThe top layer was then extracted with isopropyl acetate (440 mL×3)
  4. washwashed with water (220 mL×2)
  5. distillationThe solvents was distilled off at reduced pressure below 50° C
  6. customThe residual isopropyl acetate was azeotroped off with heptane under reduced pressure below 50° C
  7. customProduct gradually precipitated out
  8. filtrationwas filtered

Sources & evidence

ORD record
ord-3ee44e5e5d6041beaf21ee1dd2b3c837
Source dataset
uspto-grants-2016_08
Patent number
US09416110B2

Reaction notes

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