Tetrahydrofuran → Tert-butyl 4-[5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]piperidine-1-carboxylate

HRID 2095728Notes

Reaction equation

HRID 2095728 reaction equation
I[C:2]1[CH:3]=[N:4][N:5]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)[C:6]=1[CH3:7].C1COCC1.C([Mg]Cl)(C)C.CO[B:33]1[O:37][C:36]([CH3:39])([CH3:38])[C:35]([CH3:41])([CH3:40])[O:34]1>O>[CH3:7][C:6]1[N:5]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)[N:4]=[CH:3][C:2]=1[B:33]1[O:37][C:36]([CH3:39])([CH3:38])[C:35]([CH3:41])([CH3:40])[O:34]1

Participants

6

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 109757592-Methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 67004465tert-butyl 4-(4-iodo-5-methyl-1H-pyrazol-1-yl)piperidine-1-carboxylateHCID 178418918HCID 178418918, compound

Product 1

HCID 59392638Tert-butyl 4-[5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of tert-butyl 4-(4-iodo-5-methyl-1H-pyrazol-1-yl)piperidine-1-carboxylate (700.0 mg, 1.789 mmol) in THF (20 mL, 300 mmol) at rt was added 1.3 M of isopropylmagnesium chloride in THF (5.5 mL, 7.2 mmol), and the mixture was stirred for 1 h. The reaction was quenched with 2-methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.5 mL, 8.9 mmol), and allowed to stir at rt for 2 h. Water was added, and the organic solvent was removed in vacuo. The material was extracted with DCM and water. The organic layer was dry-loaded onto silica gel for column chromatography, eluting with 10% EtOAc/heptane. The fractions containing the pure product were concentrated in vacuo to afford the title compound as a white solid. 1H NMR (400 MHz, CD3OD): δ=1.30 (s, 12H), 1.48 (s, 9H), 1.84 (d, J=10.4 Hz, 2H), 1.99 (dtd, J=12.6, 12.3, 12.3, 4.5 Hz, 2H), 2.47 (s, 3H), 2.94 (br. s., 2H), 4.21 (d, J=13.6 Hz, 2H), 4.30-4.42 (m, 1H), 7.57 (s, 1H). MS (ES+): m/z=391.26/392.26/393.27 (50/100/50) [MH+]. HPLC: tR=1.70 min (polar—3 min, UPLC-ACQUITY).

Workup

  1. stirringto stir at rt for 2 h
  2. customthe organic solvent was removed in vacuo
  3. extractionThe material was extracted with DCM and water
  4. washeluting with 10% EtOAc/heptane
  5. additionThe fractions containing the pure product
  6. concentrationwere concentrated in vacuo

Sources & evidence

ORD record
ord-4ea3a09d61374bbfb5e2afb495a4f4b2
Source dataset
uspto-grants-2013_05
Patent number
US08445510B2

Reaction notes

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