tert-Butanol → (S)-tert-butyl 5-(4-chlorophenyl)-6-(1,1,1-trifluoropropan-2-yloxy)pyridin-3-ylcarbamate

HRID 1958146Notes

Reaction equation

HRID 1958146 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([O:17][C@@H:18]([CH3:23])[C:19]([F:22])([F:21])[F:20])=[N:10][CH:11]=[C:12]([CH:16]=2)C(O)=O)=[CH:4][CH:3]=1.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:31])=CC=1.C([N:43]([CH2:46]C)CC)C.[C:48]([OH:52])([CH3:51])([CH3:50])[CH3:49]>>[C:48]([O:52][C:46](=[O:31])[NH:43][C:12]1[CH:11]=[N:10][C:9]([O:17][C@@H:18]([CH3:23])[C:19]([F:22])([F:21])[F:20])=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[CH:16]=1)([CH3:51])([CH3:50])[CH3:49]

Participants

5

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 66678484(S)-5-(4-Chlorophenyl)-6-(1,1,1-trifluoropropan-2-yloxy)nicotinic acid

Product 1

HCID 67281043(S)-tert-butyl 5-(4-chlorophenyl)-6-(1,1,1-trifluoropropan-2-yloxy)pyridin-3-ylcarbamateYield 99%

Conditions

Temperature
100 °C

Procedure

(S)-5-(4-Chlorophenyl)-6-(1,1,1-trifluoropropan-2-yloxy)nicotinic acid (0.300 g, 868 μmol) was suspended in t-butanol (3.0 mL). DPPA (358 mg, 282 μl), and triethylamine (87.8 mg, 120 μl, 868 μmol) were added and the reaction mixture was stirred at 100° C. overnight. The mixture was cooled to room temperature, extracted with ethyl acetate and sodium carbonate solution, the organic phase was dried with MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 20 g, 5% to 25% ethyl acetate in heptane) to give 0.36 g (99%) of the title compound as white solid; MS (EI) 417.3 (M+H)+.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate and sodium carbonate solution
  3. dry with materialthe organic phase was dried with MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe crude material was purified by flash chromatography (silica gel, 20 g, 5% to 25% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-940d3428f1d741f0a4eb9775b1b38a38
Source dataset
uspto-grants-2013_04
Patent number
US08410107B2

Reaction notes

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