tert-Butyl 4-oxopiperidine-1-carboxylate → tert-butyl 4-(6-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-hydroxypiperidine-1-carboxylate

HRID 2378981Notes

Reaction equation

HRID 2378981 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]2[N:8]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:9]=[CH:10][C:5]2=[CH:4][CH:3]=1.[Li]C(CC)C.[O:26]=[C:27]1[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]1>C1COCC1>[Cl:1][C:2]1[N:7]=[C:6]2[N:8]([Si:11]([CH:15]([CH3:17])[CH3:16])([CH:18]([CH3:20])[CH3:19])[CH:12]([CH3:13])[CH3:14])[CH:9]=[CH:10][C:5]2=[C:4]([C:27]2([OH:26])[CH2:28][CH2:29][N:30]([C:33]([O:35][C:36]([CH3:38])([CH3:37])[CH3:39])=[O:34])[CH2:31][CH2:32]2)[CH:3]=1

Participants

5

Reactant 3

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 497589456-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridineHCID 178418400CID 53628100

Product 1

HCID 59006382tert-butyl 4-(6-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-hydroxypiperidine-1-carboxylateYield 48.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a colorless solution of 6-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (500 mg, 1.63 mmol) in THF (16 mL) was dropwise added sec-BuLi at −78° C. under N2 over 6 min, and the resulting tan solution was stirred for 2 hr. Tert-butyl 4-oxopiperidine-1-carboxylate (1.13 g, 5.70 mmol) in THF (3 mL) was dropwise added over 10 min to give a light tan solution at −78° C. under N2, and continued stirring for 2 hr. The reaction was quenched with sat. NH4Cl (30 mL), extracted with Et2O (2×50 mL). The combined organic phase was washed with brine (30 mL), dried (MgSO4), concentrated on rotary vacuo and purified on Biotage Flash Collector eluting with 20˜50% EtOAc/Hexanes (800 mL) to give the expected product, tert-butyl 4-(6-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-hydroxypiperidine-1-carboxylate (400 mg, 48%), as a light yellow solid. 1H-NMR (400 MHz, CHLOROFORM-D) δ ppm 1.25 (t, J=7.68 Hz, 18 H) 1.64 (s, 9 H) 1.94 (dt, J=15.17, 7.65 Hz, 5 H) 2.33-2.44 (m, 2 H) 3.42 (s, 2 H) 4.24 (d, J=7.05 Hz, 2 H) 6.88 (d, J=3.53 Hz, 1 H) 7.38-7.41 (m, 3 H); Mass spec. 508.25 (MH+) calc. for C26H42ClN3O3Si 507.27.

Workup

  1. customat −78° C.
  2. customover 6 min
  3. customto give a light tan solution at −78° C. under N2
  4. stirringcontinued stirring for 2 hr
  5. customThe reaction was quenched with sat. NH4Cl (30 mL)
  6. extractionextracted with Et2O (2×50 mL)
  7. washThe combined organic phase was washed with brine (30 mL)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated on rotary vacuo
  10. custompurified on Biotage Flash Collector
  11. washeluting with 20˜50% EtOAc/Hexanes (800 mL)

Sources & evidence

ORD record
ord-5d9e98a9ef7b427faa36190f3741774b
Source dataset
uspto-grants-2008_12
Patent number
US07470680B2

Reaction notes

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