Boronic Acid → (S)-4-(5-(1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-1,3,4-oxadiazol-2-yl)phenylboronic acid

HRID 18352

반응식

HRID 18352 반응식
I[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([C@@H:13]3[CH2:17][CH2:16][CH2:15][N:14]3[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[N:10][N:9]=2)=[CH:4][CH:3]=1.[B:25]1(B2OC(C)(C)C(C)(C)O2)[O:29]C(C)(C)C(C)(C)[O:26]1.CC([O-])=O.[K+].B(O)O>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:21]([O:20][C:18]([N:14]1[CH2:15][CH2:16][CH2:17][C@H:13]1[C:11]1[O:12][C:8]([C:5]2[CH:6]=[CH:7][C:2]([B:25]([OH:29])[OH:26])=[CH:3][CH:4]=2)=[N:9][N:10]=1)=[O:19])([CH3:24])([CH3:23])[CH3:22]

참가 물질

7

반응물 4

HCID 61668Boronic AcidHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 59345147(S)-tert-butyl 2-(5-(4-iodophenyl)-1,3,4-oxadiazol-2-yl)pyrrolidine-1-carboxylate

생성물 1

HCID 59345156(S)-4-(5-(1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-1,3,4-oxadiazol-2-yl)phenylboronic acid수율 22%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

A mixture of (S)-tert-butyl 2-(5-(4-iodophenyl)-1,3,4-oxadiazol-2-yl)pyrrolidine-1-carboxylate (24) (0.574 g, 1.30 mmol), bis(pinacolato)diboron (0.665 g, 2.62 mmol), KOAc (0.641 g, 6.53 mmol) and Pd(PPh3)4 (0.076 g, 0.0658 mmol) in dioxane (5 mL) was degassed with a stream of Ar for 15 minutes. The mixture was then heated at 100° C. for 12 hours, cooled to room temperature and poured into ethyl acetate/H2O. The layers were separated, the aqueous phase was re-extracted with ethyl acetate (2×) and the combined organic layers were washed (H2O, brine) and dried (Na2SO4) and filtered. The solvent was removed in vacuo and the residue purified by flash chromatography (hexane:ethyl acetate, 1:1) to give a mixture of the title boronate ester (25) and boronic acid (26). This mixture was repurified by prep HPLC (CH3CN:H2O:TFA) to afford (S)-4-(5-(1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-1,3,4-oxadiazol-2-yl)phenylboronic acid 26 as a colorless solid (0.101 g, 22%). 1HNMR (400 MHz, DMSO-d6) δ 8.31 (s, br, 2H), 7.94-8.00 (m, 4H), 5.03-5.10 (m, 1H), 3.37-3.42 (m, 2H), 2.31-2.40 (m, 1H), 1.92-2.04 (m, 3H). 1.38 (s, 3H), 1.18 (s, 6H); LCMS: Anal. Calcd. for C17H22BN3O5: 359. found: 360 (M+H)+.

후처리

  1. customwas degassed with a stream of Ar for 15 minutes
  2. temperaturecooled to room temperature
  3. additionpoured into ethyl acetate/H2O
  4. customThe layers were separated
  5. extractionthe aqueous phase was re-extracted with ethyl acetate (2×)
  6. washthe combined organic layers were washed (H2O, brine)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. customThe solvent was removed in vacuo
  10. customthe residue purified by flash chromatography (hexane:ethyl acetate, 1:1)
  11. customto give
  12. customThis mixture was repurified by prep HPLC (CH3CN:H2O:TFA)

출처 및 근거

ORD 기록
ord-27303017a5fd476888662ce5af72322c
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07741347B2

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