N,N-Bis(trimethylsilyl)trifluoroacetamide → Racemic N-((3SR,4RS)-3-(5-Bromo-2-fluorophenyl)-4-(hydroxymethyl)tetrahydrofuran-3-ylcarbamothioyl)benzamide

HRID 2060752Notes

Reaction equation

HRID 2060752 reaction equation
[NH2:1][C:2]1([C:9]2[CH:14]=[C:13]([Br:15])[CH:12]=[CH:11][C:10]=2[F:16])[CH2:6][O:5][CH2:4][CH:3]1[CH2:7][OH:8].C[Si](N([Si](C)(C)C)C(=O)C(F)(F)F)(C)C.[C:32]([N:40]=[C:41]=[S:42])(=[O:39])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>O1CCCC1.C(OCC)(=O)C>[Br:15][C:13]1[CH:12]=[CH:11][C:10]([F:16])=[C:9]([C:2]2([NH:1][C:41]([NH:40][C:32](=[O:39])[C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=3)=[S:42])[CH:3]([CH2:7][OH:8])[CH2:4][O:5][CH2:6]2)[CH:14]=1

Participants

6

Reactant 3

HCID 65279N,N-Bis(trimethylsilyl)trifluoroacetamideHCID 68284Benzoyl isothiocyanateHCID 66847662Racemic ((3RS,4SR)-4-Amino-4-(5-bromo-2-fluorophenyl)tetrahydrofuran-3-yl)methanol

Product 1

HCID 76656268Racemic N-((3SR,4RS)-3-(5-Bromo-2-fluorophenyl)-4-(hydroxymethyl)tetrahydrofuran-3-ylcarbamothioyl)benzamideYield 94%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of racemic ((3RS,4SR)-4-amino-4-(5-bromo-2-fluorophenyl)tetrahydrofuran-3-yl)methanol (75 g, 259 mmol) in tetrahydrofuran (1.3 L) at 25° C. under a nitrogen atmosphere is added dropwise bis(trimethylsilyl)trifluoroacetamide (76.3 mL, 259 mmol) keeping the internal temperature below 30° C. The reaction is stirred at 25° C. for 30 minutes. Benzoyl isothiocyanate (38.4 mL, 284 mmol) is added over 10 minutes keeping internal temperature below 35° C. and the reaction is stirred at 25° C. for 30 min. The reaction mixture is diluted with ethyl acetate (500 mL) and is washed three times with 1 N HCl (3×500 mL), followed by water and brine. The solution is dried over magnesium sulfate and the solvent is removed under reduced pressure. The residue is purified by silica gel chromatography using a linear gradient of 25% to 50% ethyl acetate in hexanes to give the title compound (110 g, 94%). ES/MS m/e (79Br/81Br) 453, 455 (M+1).

Workup

  1. customthe internal temperature below 30° C
  2. customtemperature below 35° C.
  3. stirringthe reaction is stirred at 25° C. for 30 min
  4. washis washed three times with 1 N HCl (3×500 mL)
  5. dry with materialThe solution is dried over magnesium sulfate
  6. customthe solvent is removed under reduced pressure
  7. customThe residue is purified by silica gel chromatography

Sources & evidence

ORD record
ord-fbea1283f31a4f14a0210d25349360e4
Source dataset
uspto-grants-2012_10
Patent number
US08278441B2

Reaction notes

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