Acetic Acid → 8-[8-(Tert-butyl-dimethyl-silanyloxymethyl)-naphthalen-1-ylmethyl]-1-(4-fluoro-phenyl)-1,3,8-triaza-spiro[4.5]decan-4-one

HRID 1623035Notes

Reaction equation

HRID 1623035 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3([CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)[C:11](=[O:18])[NH:10][CH2:9]2)=[CH:4][CH:3]=1.[C:19]([SiH2:23][O:24][C:25]([CH3:39])([CH3:38])[C:26]1[CH:27]=[CH:28][CH:29]=[C:30]2[C:35]=1[C:34]([CH:36]=O)=[CH:33][CH:32]=[CH:31]2)([CH3:22])([CH3:21])[CH3:20].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[C:19]([SiH2:23][O:24][C:25]([CH3:39])([CH3:38])[C:26]1[CH:27]=[CH:28][CH:29]=[C:30]2[C:35]=1[C:34]([CH2:36][N:15]1[CH2:14][CH2:13][C:12]3([N:8]([C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=4)[CH2:9][NH:10][C:11]3=[O:18])[CH2:17][CH2:16]1)=[CH:33][CH:32]=[CH:31]2)([CH3:22])([CH3:21])[CH3:20]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 939151-(4-Fluorophenyl)-1,3,8-triazaspiro(4.5)decan-4-oneHCID 5049666Sodium triacetoxyborohydrideHCID 1373285318-(Tert-butyl-dimethyl-silanyloxymethyl)-naphthalene-1-carbaldehyde

Product 1

HCID 1373285338-[8-(Tert-butyl-dimethyl-silanyloxymethyl)-naphthalen-1-ylmethyl]-1-(4-fluoro-phenyl)-1,3,8-triaza-spiro[4.5]decan-4-one

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

1-(4-Fluoro-phenyl)-1,3,8-triaza-spiro[4.5]decan-4-one (0.056 g, 0.22 mmol) and 8-(tert-butyl-dimethyl-silanyloxymethyl)-naphthalene-1-carbaldehyde (0.067 g, 0.22 mmol) were dissolved in dry 1,2-dichloroethane (5 mL). To the reaction mixture was added crashed 4 A Molecular Sieve (0.028 g), a catalytic amount of glacial acetic acid. The reaction mixture was stirred at room temperature for 1 hr and it was then added at room temperature sodium triacetoxyborohydride (0.071 g, 0.33 mmol) under nitrogen atmosphere and the reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was then partitioned with water and dichloromethane. The organic layer was washed with brine, dried with Na2SO4, filtered and the solvent evaporated in vacuo to yield a crude oil. The crude oil was purified via semi-preparative HPLC (aqueous 0.5% TFA/acetonitrile) to yield crude 8-[8-(tert-butyl-dimethyl-silanyloxymethyl)-naphthalen-1-ylmethyl]-1-(4-fluoro-phenyl)-1,3,8-triaza-spiro[4.5]decan-4-one which was directly used to the next step.

Workup

  1. additionTo the reaction mixture was added
  2. stirringthe reaction mixture was stirred at room temperature for 18 hours
  3. customThe reaction mixture was then partitioned with water and dichloromethane
  4. washThe organic layer was washed with brine
  5. dry with materialdried with Na2SO4
  6. filtrationfiltered
  7. customthe solvent evaporated in vacuo
  8. customto yield a crude oil
  9. customThe crude oil was purified via semi-preparative HPLC (aqueous 0.5% TFA/acetonitrile)

Sources & evidence

ORD record
ord-5c2a094a008446c29d08970e08ffa055
Source dataset
uspto-grants-2014_07
Patent number
US08778956B2

Reaction notes

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