Triethylamine → HCID 86707799, compound

HRID 2174392Notes

Reaction equation

HRID 2174392 reaction equation
C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:8])C=CC=CC=1.[F:18][C:19]1([C:26]2[CH:31]=[CH:30][C:29]([C:32]3[CH2:36][C:35]([C:41]4[CH:46]=[C:45]([Cl:47])[C:44]([Cl:48])=[C:43]([Cl:49])[CH:42]=4)([C:37]([F:40])([F:39])[F:38])[O:34][N:33]=3)=[CH:28][CH:27]=2)[CH2:22][CH:21](C(O)=O)[CH2:20]1.C([N:52]([CH2:55]C)CC)C.[CH3:57][Si:58]([CH3:63])([CH3:62])[CH2:59][CH2:60][OH:61]>C1COCC1>[F:18][C:19]1([C:26]2[CH:27]=[CH:28][C:29]([C:32]3[CH2:36][C:35]([C:41]4[CH:46]=[C:45]([Cl:47])[C:44]([Cl:48])=[C:43]([Cl:49])[CH:42]=4)([C:37]([F:40])([F:39])[F:38])[O:34][N:33]=3)=[CH:30][CH:31]=2)[CH2:22][CH:21]([NH:52][C:55](=[O:8])[O:61][CH2:60][CH2:59][Si:58]([CH3:63])([CH3:62])[CH3:57])[CH2:20]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 180132-(Trimethylsilyl)ethanolHCID 199401P,P-Diphenylphosphinic azideHCID 86707793HCID 86707793, compound

Product 1

HCID 86707799HCID 86707799, compoundYield 53.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
64 °C

Procedure

Diphenyl phosphoryl azide (93 μL, 0.43 mmol) is added to 3-fluoro-3-(4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)phenyl)cyclobutanecarboxylic acid (from Preparation 6 and Preparation 7, 200 mg, 0.39 mmol) along with triethylamine (66 μL, 0.47 mmol) and 2-trimethylsilylethanol (60 μL, 0.41 mmol) in THF (4.0 mL) and the mixture heated to 64° C. for 16 hours. After cooling to room temperature the mixture is partitioned between water (10 mL) and EtOAc (10 mL). The organics are separated, dried over MgSO4, filtered and evaporated to give a yellow oil, which is further purified using on regular silica from neat heptane to neat EtOAc to give the title compound (130 mg): 1H NMR (CDCl3) δ: 7.64-7.60 (4H, m), 7.46-7.44 (2H, m), 4.83 (1H, m), 4.14-4.09 (2H, m), 4.05 (2H, d), 3.64 (2H, d), 2.97-2.87 (2H, m), 2.66-2.56 (2H, m), 1.26-1.20- (1H, m), 0.96-0.91 (2H, m), 0.00 (9H, s).

Workup

  1. temperatureAfter cooling to room temperature the mixture
  2. customis partitioned between water (10 mL) and EtOAc (10 mL)
  3. customThe organics are separated
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customto give a yellow oil, which
  8. customis further purified

Sources & evidence

ORD record
ord-2564406adaad4d758a038ccd75ff7d6a
Source dataset
uspto-grants-2015_06
Patent number
US09061013B2

Reaction notes

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