tert-Butanol → Tert-butyl 5-(trifluoromethyl)thiophen-2-ylcarbamate

HRID 588067Notes

Reaction equation

HRID 588067 reaction equation
[F:1][C:2]([F:12])([F:11])[C:3]1[S:7][C:6](C(O)=O)=[CH:5][CH:4]=1.C([N:15]([CH2:18]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:27])C=CC=CC=1.[CH3:37][C:38]([OH:41])([CH3:40])[CH3:39]>>[F:12][C:2]([F:1])([F:11])[C:3]1[S:7][C:6]([NH:15][C:18](=[O:27])[O:41][C:38]([CH3:40])([CH3:39])[CH3:37])=[CH:5][CH:4]=1

Participants

5

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 20490515-(Trifluoromethyl)thiophene-2-carboxylic acid

Product 1

HCID 86718387Tert-butyl 5-(trifluoromethyl)thiophen-2-ylcarbamate

Conditions

Temperature
90 °C

Procedure

To 5-(trifluoromethyl)thiophene-2-carboxylic acid in tBuOH (50 mL) was added triethylamine (1.53 mL, 11 mmol) and diphenylphosphoryl azide (DPPA) (2.4 mL, 11 mmol). This mixture was heated to 90° C., and was stirred overnight (ca. 16 hours). Thin layer chromatography (TLC) indicated that the reaction was complete. The solvent was removed under reduced pressure, the residue was dissolved in ethyl acetate (EtOAc) and washed 1× with NaHCO3 aq sat, 1× with citric acid (10% aqueous), and 1× brine. The solution was dried over MgSO4, filtered and concentrated. After silica gel chromatography (5 to 20% EtOAc/hexanes) the title compound was afforded (1.46 g, 44% over 3 steps) as a yellow/orange solid, mp 118-120° C.; Rf=0.31 (10% EtOAc/hex); 1H NMR (DMSO-d6) δ 11.03 (br s, 1H), 7.38 (app d, 1H, J=4.1 Hz), 6.51 (app d, 1H, J=3.3 Hz), 1.49 (s, 9H); GCMS (EI) m/z 267 (M+).

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe residue was dissolved in ethyl acetate (EtOAc)
  3. washwashed 1× with NaHCO3 aq
  4. dry with materialThe solution was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-3cc06a9e2b7e4b10b3014c4f675fa48c
Source dataset
uspto-grants-2016_01
Patent number
US09227957B2

Reaction notes

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