n-Butyl lithium → HCID 57546195, compound

HRID 913955Notes

Reaction equation

HRID 913955 reaction equation
[Li+].[CH3:2]CC[CH2-].[Cl:6][C:7]1[CH:15]=[C:14]([CH:16]([O:19][CH2:20][C:21]2([C:34]3[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=3)[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]2)[CH:17]=O)[C:13]2[C:9](=[CH:10][N:11]([CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[N:12]=2)[CH:8]=1>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1.CCOCC>[Cl:6][C:7]1[CH:15]=[C:14]([CH:16]([O:19][CH2:20][C:21]2([C:34]3[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=3)[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:31])([CH3:33])[CH3:32])=[O:28])[CH2:23][CH2:22]2)[CH:17]=[CH2:2])[C:13]2[C:9](=[CH:10][N:11]([CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[N:12]=2)[CH:8]=1

Participants

6

Reactant 2

HCID 61028n-Butyl lithiumHCID 57546061HCID 57546061, compound

Product 1

HCID 57546195HCID 57546195, compoundYield 30.4%

Reagents, catalysts & solvents 3

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of methyltriphenylphosphoniumbromide (470 mg, 1.314 mmol) in THF (17 ml) was added N-BUTYLLITHIUM (0.526 ml, 1.314 mmol). The ice bath was removed and the suspension was stirred for 10 min. To this was added tert-butyl 4-((1-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)-2-oxoethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (277 mg, 0.438 mmol) in 2.5 mL THF. The reaction was allowed to stir 1 hour before diluted with ether (100 mL) and filtered out the solid, the ether layer was washed with water, brine and dried over magnesium sulfate, filtered and concentrated. It was then purified by Biotage LC (20-25% EtOAc/Hex) to give title compound (84 mg, 0.133 mmol, 30.4% yield) as light yellow foam solid. 1H-NMR (CDCl3, 500 MHz) δ 7.98 (s, 1H), 7.49 (d, J=1.8 Hz, 1H), 7.29 (m, 2H), 7.00 T, J=8.8 Hz, 2H), 6.85 (s, 1H), 5.88 (ddd, J=17.2, 10.6, 5.9 Hz, 1H), 5.63(d, J=4.0 Hz, 1H), 5.60 (d, J=3.7 Hz, 1H), 5.30 (d, J=5.5 Hz, 1H), 5.23 (d, J=17.2 Hz, 1H), 5.02 (d, J=10.3 Hz, 1H), 3.69 (m, 2H), 3.58 (t, J=8.4 Hz, 2H), 3.42 (AB, Δν=28.5 Hz, J=8.8 Hz, 2H), 3.04 (m, 2H), 1.80-2.25 (m,4H), 1.41 (s, 9H), 0.88 (t, J=9.2 Hz, 2H), −0.07 (s, 9H). LC/MS (HPLC method 3): tR=4.43 min, 630.3(MH)+.

Workup

  1. customThe ice bath was removed
  2. stirringto stir 1 hour
  3. filtrationfiltered out the solid
  4. washthe ether layer was washed with water, brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customIt was then purified by Biotage LC (20-25% EtOAc/Hex)

Sources & evidence

ORD record
ord-099b4dee012140f9b4211da2ee866c5d
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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