Trifluoroacetic acid → 2-Fluoro-2-(3-((4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methyl)phenyl)acetaldehyde

HRID 471061Notes

Reaction equation

HRID 471061 reaction equation
[F:1][CH:2]([C:5]1[CH:6]=[C:7]([CH:30]=[CH:31][CH:32]=1)[CH2:8][N:9]1[CH2:29][CH2:28][C:12]2([O:17][CH2:16][CH2:15][N:14]([C:18]([C:20]3[N:21]=[C:22]([CH:25]([CH3:27])[CH3:26])[S:23][CH:24]=3)=[O:19])[CH2:13]2)[CH2:11][CH2:10]1)[CH2:3][OH:4].FC(F)(F)C(O)=O.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[F:1][CH:2]([C:5]1[CH:32]=[CH:31][CH:30]=[C:7]([CH2:8][N:9]2[CH2:29][CH2:28][C:12]3([O:17][CH2:16][CH2:15][N:14]([C:18]([C:20]4[N:21]=[C:22]([CH:25]([CH3:26])[CH3:27])[S:23][CH:24]=4)=[O:19])[CH2:13]3)[CH2:11][CH2:10]2)[CH:6]=1)[CH:3]=[O:4]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 159087TriacetoxyperiodinaneHCID 67292595(9-(3-(1-Fluoro-2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

Product 1

HCID 579890482-Fluoro-2-(3-((4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methyl)phenyl)acetaldehyde

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (9-(3-(1-fluoro-2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone (example 39, step f) (0.213 g) in DCM (5 mL) was cooled in ice-water and treated with trifluoroacetic acid (0.053 mL) and stirred for 5 minutes. Dess-Martin periodinane (0.296 g) was added and the mixture was removed from the cooling bath and stirred at room temperature for 20 minutes. More Dess-Martin periodinane (0.295 g) was added and the mixture was stirred at room temperature for an additional 30 minutes. The reaction was then quenched by the addition of saturated sodium thiosulphate solution (5 mL), saturated sodium bicarbonate solution (5 mL) and ethyl acetate (5 mL), and the resulting two-phase mixture was stirred for 10 minutes. The mixture was then extracted twice with ethyl acetate, and the combined organic extracts washed with brine. Acetic acid (0.1 mL) was added, then the acidified extracts were dried over anhydrous magnesium sulphate and concentrated in vacuo to afford the crude subtitled product as an off-white foam. Yield 0.240 g.

Workup

  1. customthe mixture was removed from the cooling bath
  2. stirringstirred at room temperature for 20 minutes
  3. additionMore Dess-Martin periodinane (0.295 g) was added
  4. stirringthe mixture was stirred at room temperature for an additional 30 minutes
  5. customThe reaction was then quenched by the addition of saturated sodium thiosulphate solution (5 mL), saturated sodium bicarbonate solution (5 mL) and ethyl acetate (5 mL)
  6. stirringthe resulting two-phase mixture was stirred for 10 minutes
  7. extractionThe mixture was then extracted twice with ethyl acetate
  8. washthe combined organic extracts washed with brine
  9. additionAcetic acid (0.1 mL) was added
  10. dry with materialthe acidified extracts were dried over anhydrous magnesium sulphate
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d4712536aa6b4af78b43fb81d8a8904d
Source dataset
uspto-grants-2014_01
Patent number
US08629271B2

Reaction notes

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