Triethylamine → HCID 86698454, compound

HRID 1484649Notes

Reaction equation

HRID 1484649 reaction equation
[CH3:1][C:2]1([CH3:25])[C:6]2[C:7]([O:17][C:18]3[N:23]=[CH:22][C:21]([NH2:24])=[CH:20][CH:19]=3)=[CH:8][C:9](OC(F)(F)F)=[C:10]([CH3:11])[C:5]=2[O:4][CH2:3]1.C(N(CC)CC)C.[CH3:33][C:34]([O:37][C:38]([NH:40][C@H:41]([CH2:45][CH3:46])[C:42](O)=[O:43])=[O:39])([CH3:36])[CH3:35].C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.C([O-])([O-])=O.[Na+].[Na+]>C(OCC)(=O)C>[CH3:25][C:2]1([CH3:1])[C:6]2[C:7]([O:17][C:18]3[N:23]=[CH:22][C:21]([NH:24][C:42]([C@H:41]([NH:40][C:38](=[O:39])[O:37][C:34]([CH3:36])([CH3:35])[CH3:33])[CH2:45][CH3:46])=[O:43])=[CH:20][CH:19]=3)=[CH:8][CH:9]=[C:10]([CH3:11])[C:5]=2[O:4][CH2:3]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 111923Propylphosphonic anhydrideHCID 2755936(2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acidHCID 86698455HCID 86698455, compound2×

Product 1

HCID 86698454HCID 86698454, compoundYield 86.4%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

6-{[3,3,7-Trimethyl-6-(trifluoromethoxy)-2,3-dihydro-1-benzofuran-4-yl]oxy}pyridin-3-amine (Intermediate 29, 405 mg, 1.27 mmol) was suspended in ethyl acetate (4 mL). Triethylamine (0.44 ml, 3.175 mmol) was added followed by the addition of (2R)-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)butanoic acid (258 mg, 1.27 mmol). The resulting suspension was cooled to 0° C. and T3P 50% w/w solution in ethyl acetate (1.4 mmol) was added drop wise. The reaction mixture was stirred at 0° C. for 1 hour and then warmed to room temperature and stirred for a further hour. An aqueous saturated solution of Na2CO3 was added and the mixture stirred for 10 min. Two phases were separated and the organic layer was washed with water and brine, dried over Na2SO4 and evaporated to dryness. The residue was purified by flash chromatography on silica gel using cyclohexane/ethyl acetate 80:20 to cyclohexane/ethyl acetate 70:30 as eluents affording the title compound (0.50 g) as white foam.

Workup

  1. temperaturewarmed to room temperature
  2. stirringstirred for a further hour
  3. stirringthe mixture stirred for 10 min
  4. customTwo phases were separated
  5. washthe organic layer was washed with water and brine
  6. dry with materialdried over Na2SO4
  7. customevaporated to dryness
  8. customThe residue was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-1683fa6203bf4e5ea58a5b2292d8a33f
Source dataset
uspto-grants-2016_08
Patent number
US09422272B2

Reaction notes

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