(Trifluoromethyl)trimethylsilane → HCID 67111469, compound

HRID 1177485Notes

Reaction equation

HRID 1177485 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[C:10]1[S:11][C:12]2[C:17]([N:18]=1)=[CH:16][CH:15]=[C:14]([C:19]1([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:21][CH2:20]1)[N:13]=2)[CH:5]=[O:6].C[Si](C)(C)[C:30]([F:33])([F:32])[F:31].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[F:31][C:30]([F:33])([F:32])[CH:5]([C:4]1[CH:7]=[CH:8][C:9]([C:10]2[S:11][C:12]3[C:17]([N:18]=2)=[CH:16][CH:15]=[C:14]([C:19]2([C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=4)[CH2:20][CH2:21]2)[N:13]=3)=[C:2]([F:1])[CH:3]=1)[OH:6]

Participants

5

Reactant 3

HCID 552549(Trifluoromethyl)trimethylsilaneHCID 2724141Tetrabutylammonium FluorideHCID 591749073-Fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)benzaldehyde

Product 1

HCID 67111469HCID 67111469, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture of 3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)benzaldehyde (2.00 g, 5.34 mmol) and trimethyl(trifluoromethyl)silane (0.911 g, 6.41 mmol) in 20 mL THF under nitrogen at 0° C. was added TBAF 1.0 M in THF (0.534 mL, 0.534 mmol). The reaction mixture became immediately dark brown and homogeneous. The water bath was removed and the reaction mixture was allowed to stir for 3 h. 1N aq. HCl (20 mL) was added and the reaction mixture allowed to stir overnight. The reaction mixture was partitioned between water and DCM. The aqueous layer was extracted with DCM, and the combined organics were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The material was treated with DCM and passed through a Redi-Sep® pre-packed silica gel column (40 g) using 0-20% EtOAc/hexane. The product-containing fractions were concentrated to afford racemic 2,2,2-trifluoro-1-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)ethanol as a pale yellow foam. The racemic mixture were separated by Multigram II SFC (Column: Chiralpak ADH (21×250 mm, 5 um); A=supercritical CO2; B=Isopropanol; 30% B, 65 mL/min total flow, 40° C., 100 bar outlet pressure) to give (R)-2,2,2-trifluoro-1-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)ethanol and (S)-2,2,2-trifluoro-1-(3-fluoro-4-(5-(1-phenylcyclopropyl)-thiazolo[5,4-b]pyridine-2-yl)phenyl)ethanol. MS (ESI) m/z: calculated: 444.1; Observed: 445.1 (M++1).

Workup

  1. customThe water bath was removed
  2. addition1N aq. HCl (20 mL) was added
  3. stirringto stir overnight
  4. customThe reaction mixture was partitioned between water and DCM
  5. extractionThe aqueous layer was extracted with DCM
  6. dry with materialthe combined organics were dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. additionThe material was treated with DCM
  10. concentrationThe product-containing fractions were concentrated

Sources & evidence

ORD record
ord-dcc66b3348454256963625e8afe5a622
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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