Hydrochloric Acid → HCID 66661172, compound

HRID 1913318Notes

Reaction equation

HRID 1913318 reaction equation
[F:1][C:2]([F:13])([CH3:12])[CH2:3][C@H:4]([N:9]=[C:10]=[O:11])[C:5]([O:7]C)=[O:6].C(=O)([O-])O.[Na+].[CH2:19]1[C:24]2([CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)[CH2:23][CH2:22][NH:21][CH2:20]1.[Li+].[OH-].Cl>C1COCC1.C(OCC)(=O)C>[CH2:19]1[C:24]2([CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)[CH2:23][CH2:22][N:21]([C:10]([NH:9][C@@H:4]([CH2:3][C:2]([F:13])([F:1])[CH3:12])[C:5]([OH:7])=[O:6])=[O:11])[CH2:20]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 4174123-Azaspiro(5.5)undecane hydrochlorideHCID 516892Sodium BicarbonateHCID 57946243Methyl (S)-4,4-difluoro-2-isocyanatopentanoate

Product 1

HCID 66661172HCID 66661172, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

252 mg (1.3 mmol) of the isocyanate from example 7 were dissolved at 0° C. in 5 ml of THF and admixed with 109 mg (3.25 mmol, 2.5 eq.) of sodium hydrogencarbonate and 209 mg (1.37 mmol, 1.05 eq.) of 3-azaspiro[5.5]undecane. The mixture was stirred overnight, precipitated salts were removed and the reaction mixture was treated directly with 2.5 ml of 1 M LiOH solution (2.5 mmol, 1.9 eq.). The reaction was monitored by HPLC-MS. When the mass peak of the reactant had disappeared completely, the mixture was acidified cautiously with dilute HCl and the product was isolated by extraction with ethyl acetate, drying of the organic phase over sodium sulfate and concentration under reduced pressure. Yield: 440 mg (quantitative). The crude product was used directly in the amide coupling which follows.

Workup

  1. customprecipitated salts
  2. customwere removed
  3. dry with materialdrying of the organic phase over sodium sulfate and concentration under reduced pressure

Sources & evidence

ORD record
ord-913ce297e0d74b2692a1d17977f7b5e1
Source dataset
uspto-grants-2013_12
Patent number
US08609681B2

Reaction notes

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