Hydrochloric Acid → HCID 90412924, compound

HRID 1526658Notes

Reaction equation

HRID 1526658 reaction equation
[NH2:1][C:2]1[O:3][C@H:4]2[C@@H:6]([C@:7]([C:12]3[CH:13]=[C:14]([NH:20][C:21]([C:23]4[CH:32]=[CH:31][C:26]([C:27](=N)[O:28][CH3:29])=[CH:25][N:24]=4)=[O:22])[CH:15]=[C:16]([F:19])[C:17]=3[F:18])([CH:9]([F:11])[F:10])[N:8]=1)[CH2:5]2.Cl.C(=O)(O)[O-:35].[Na+]>[OH-].[Na+]>[NH2:1][C:2]1[O:3][C@@H:4]2[C@H:6]([C@@:7]([C:12]3[CH:13]=[C:14]([NH:20][C:21]([C:23]4[CH:32]=[CH:31][C:26]([C:27]([O:28][CH3:29])=[O:35])=[CH:25][N:24]=4)=[O:22])[CH:15]=[C:16]([F:19])[C:17]=3[F:18])([CH:9]([F:11])[F:10])[N:8]=1)[CH2:5]2

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 90413302HCID 90413302, compound

Product 1

HCID 90412924HCID 90412924, compoundYield 59.5%

Reagents, catalysts & solvents 1

HCID 14798Sodium HydroxideSolvent

Procedure

Methyl 6-((3-((1R,5S,6R)-3-amino-5-(difluoromethyl)-2-oxa-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4,5-difluorophenyl)carbamoyl)nicotinimidate (0.050 g, 0.111 mmol) was dissolved in hydrochloric acid (2N, 5 mL, 10.00 mmol) and stirred at room temperature. After 15 minutes, the reaction mixture was neutralized with 1 N sodium hydroxide (10 mL). A solution of aqueous saturated sodium bicarbonate (5 mL) was added and the mixture stirred for 10 minutes. The suspension was filtered and the solid was washed with water (10 mL). The solid was further purified by silica gel chromatography [10-90% (2% NH4OH in 3:1 ethyl acetate: ethanol) in hexane] to give the title compound (0.0298 g, 0.066 mmol, 59.5% yield). MS m/z=452.9 [M+H]+. 1H NMR (CHLOROFORM-d) Shift: 9.75 (s, 1H), 9.04 (dd, J=2.0, 0.7 Hz, 1H), 8.48 (dd, J=8.0, 2.0 Hz, 1H), 8.26 (dd, J=8.1, 0.7 Hz, 1H), 7.99 (ddd, J=11.7, 7.0, 2.8 Hz, 1H), 7.22-7.28 (m, 1H), 6.23 (td, J=55.8, 0.9 Hz, 1H), 5.17 (br. s., 2H), 4.01 (s, 3H), 3.92 (td, J=6.8, 2.6 Hz, 1H), 1.80-1.92 (m, 1H), 1.40-1.49 (m, 1H), 0.90-1.03 (m, 1H)

Workup

  1. stirringthe mixture stirred for 10 minutes
  2. filtrationThe suspension was filtered
  3. washthe solid was washed with water (10 mL)
  4. customThe solid was further purified by silica gel chromatography [10-90% (2% NH4OH in 3:1 ethyl acetate: ethanol) in hexane]

Sources & evidence

ORD record
ord-4be3e3b4a5884cbfa7cd5cf46e8648a6
Source dataset
uspto-grants-2015_07
Patent number
US09085576B2

Reaction notes

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