Tetrahydrofuran → (S)-1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

HRID 2279723Notes

Reaction equation

HRID 2279723 reaction equation
C([Mg]Cl)(C)C.C1COCC1.[CH3:11][C:12]1([CH3:24])[O:16][C@@H:15]([CH2:17][N:18]2[CH:22]=[C:21](I)[CH:20]=[N:19]2)[CH2:14][O:13]1.CO[B:27]1[O:31][C:30]([CH3:33])([CH3:32])[C:29]([CH3:35])([CH3:34])[O:28]1>>[CH3:11][C:12]1([CH3:24])[O:16][C@@H:15]([CH2:17][N:18]2[CH:22]=[C:21]([B:27]3[O:31][C:30]([CH3:33])([CH3:32])[C:29]([CH3:35])([CH3:34])[O:28]3)[CH:20]=[N:19]2)[CH2:14][O:13]1

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 109757592-Methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 670044251-{[(4S)-2,2-Dimethyl-1,3-dioxolan-4-yl]methyl}-4-iodo-1H-pyrazole2×HCID 178418918HCID 178418918, compound

Product 1

HCID 67253006(S)-1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleYield 53%

Procedure

Isopropylmagnesium chloride in THF (2.0 M, 6.91 mL, 13.82 mmol) was added to a solution of 1-{[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-4-iodo-1H-pyrazole (Compound 5F, 2.13 g, 6.91 mmol) in THF (60 mL, 800 mmol) at rt. After 10 minutes, the mixture was treated with 2-Methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3.40 mL, 20.74 mmol) and stirred for an additional 20 minutes at rt. The reaction was then quenched with sat. NH4Cl and the mixture was concentrated in vacuo to a solid. The crude product was dissolved in DCM, washed with water (2×), dried with sodium sulfate, filtered and concentrated in vacuo to a clear oil. The crude material was purified using a Teledyne ISCO Combiflash® Rf system [20% EtOAc/hexanes] to afford 1.12 g of the title compound (53%). 1H NMR (400 MHz, CD3OD) δ 7.74 (s, 1H), 7.50 (s, 1H), 4.36-4.44 (m, 1H), 4.21-4.34 (m, 2H), 4.05 (dd, J=6.3, 8.6 Hz, 1H), 3.73 (dd, J=5.9, 8.7 Hz, 1H), 1.31 (d, J=8.6 Hz, 6H), 1.25 (s, 12H). MS (ESI): m/z 309.00 [M+H]+. UPLC: tR=1.42 min (UPLC-TOF: polar—3 min).

Workup

  1. customThe reaction was then quenched with sat. NH4Cl
  2. concentrationthe mixture was concentrated in vacuo to a solid
  3. dissolutionThe crude product was dissolved in DCM
  4. washwashed with water (2×)
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo to a clear oil
  8. customThe crude material was purified

Sources & evidence

ORD record
ord-ee12c6e042444ef7ba633fc972f747b9
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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