1-Hydroxybenzotriazole → HCID 56941482, compound

HRID 1529575Notes

Reaction equation

HRID 1529575 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([F:11])[CH:10]=1)[C:5]([OH:7])=O.[O:12]([CH2:19][C:20]1[O:21][C:22]2[CH2:23][NH:24][CH2:25][CH2:26][C:27]=2[N:28]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C=O)C.O>[F:11][C:9]1[CH:8]=[C:4]([CH:3]=[C:2]([F:1])[CH:10]=1)[C:5]([N:24]1[CH2:25][CH2:26][C:27]2[N:28]=[C:20]([CH2:19][O:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[O:21][C:22]=2[CH2:23]1)=[O:7]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 1012653,5-Difluorobenzoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66609262HCID 66609262, compound

Product 1

HCID 56941482HCID 56941482, compoundYield 54%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

3,5-Difluorobenzoic acid (0.082 g, 0.52 mmol) was added to a stirred solution of 4,5,6,7-tetrahydro-2-(phenoxymethyl)-oxazolo[5,4-c]pyridine (0.10 g, 0.43 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.10 g, 0.52 mmol), 1-hydroxybenzotriazole (0.070 g, 0.52 mmol) and N,N-diisopropylethylamine (0.15 mL, 0.87 mmol) in anhydrous DMF (2.2 mL) under N2. The reaction mixture was stirred at room temperature for 16 hours, diluted with H2O and extracted with AcOEt. The organic layer was separated, extracted with brine, dried (Na2SO4), filtered and the solvent evaporated in vacuo. The crude product was purified by flash column chromatography (silica; 7 N solution of ammonia in MeOH in DCM 0/100 to 5/95). The desired fractions were collected and the solvents evaporated in vacuo to yield 5-(3,5-difluorobenzoyl)-4,5,6,7-tetrahydro-2-(phenoxymethyl)-oxazolo[5,4-c]pyridine (0.086 g, 53% yield) as a colorless oil. C20H16F2N2O3. (mixture of rotamers 65:35) 1H NMR (500 MHz, CDCl3) δ ppm 2.71 (br. s., 1.3 H), 2.79 (br. s., 0.7 H), 3.66 (br. s., 1.3 H), 4.02 (br. s., 0.7 H), 4.50 (br. s., 0.7 H), 4.80 (br. s., 1.3 H), 5.13 (br. s., 2 H), 6.82-6.95 (m, 1 H), 6.95-7.09 (m, 5 H), 7.31 (t, J=7.8 Hz, 2 H).

Workup

  1. extractionextracted with AcOEt
  2. customThe organic layer was separated
  3. extractionextracted with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customthe solvent evaporated in vacuo
  7. customThe crude product was purified by flash column chromatography (silica; 7 N solution of ammonia in MeOH in DCM 0/100 to 5/95)
  8. customThe desired fractions were collected
  9. customthe solvents evaporated in vacuo

Sources & evidence

ORD record
ord-6c3195399f3141349d28d628ca4606a1
Source dataset
uspto-grants-2015_07
Patent number
US09090632B2

Reaction notes

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