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Lithium Chloride → 4-{hydroxy-[5-triisopropylsilanyl-2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-methyl}-4-methyl-piperidine-1-carboxylic acid tert-butyl ester

HRID 1677429
Notes
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Reaction equation

HRID 1677429 reaction equation
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([C:11]3[CH:16]=[C:15]([O:17][CH3:18])[C:14]([O:19][CH3:20])=[C:13]([O:21][CH3:22])[CH:12]=3)[N:9]=2)[N:4]([Si:23]([CH:30]([CH3:32])[CH3:31])([CH:27]([CH3:29])[CH3:28])[CH:24]([CH3:26])[CH3:25])[CH:3]=1.C([Mg]Cl)(C)C.[Li+].[Cl-].[C:40]([O:44][C:45]([N:47]1[CH2:52][CH2:51][C:50]([CH:54]=[O:55])([CH3:53])[CH2:49][CH2:48]1)=[O:46])([CH3:43])([CH3:42])[CH3:41]>C1COCC1>[NH4+:4].[OH-:17].[C:40]([O:44][C:45]([N:47]1[CH2:52][CH2:51][C:50]([CH:54]([OH:55])[C:2]2[C:10]3[C:5](=[N:6][CH:7]=[C:8]([C:11]4[CH:16]=[C:15]([O:17][CH3:18])[C:14]([O:19][CH3:20])=[C:13]([O:21][CH3:22])[CH:12]=4)[N:9]=3)[N:4]([Si:23]([CH:30]([CH3:32])[CH3:31])([CH:27]([CH3:29])[CH3:28])[CH:24]([CH3:26])[CH3:25])[CH:3]=2)([CH3:53])[CH2:49][CH2:48]1)=[O:46])([CH3:43])([CH3:42])[CH3:41]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 433294Lithium ChlorideHCID 22248051tert-Butyl 4-formyl-4-methylpiperidine-1-carboxylateHCID 595405257-iodo-5-triisopropylsilanyl-2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazineHCID 178418918HCID 178418918, compound

Product 2

HCID 14923Ammonium Hydroxide
HCID 59540603
4-{hydroxy-[5-triisopropylsilanyl-2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-methyl}-4-methyl-piperidine-1-carboxylic acid tert-butyl ester
Yield 236.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a −78° C. solution of 7-iodo-5-triisopropylsilanyl-2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazine (680 mg, 1.2 mmol) in THF (4 mL) was added iPrMgCl.LiCl (2.7 mL, 1.3 M in THF, 3.5 mmol) dropwise along the side of the flask. The reaction was stirred for 10 min at −78° C. and a solution of 4-formyl-4-methyl-piperidine-1-carboxylic acid tert-butyl ester (700 mg, 3.1 mmol) in THF (4 mL) was added slowly along the side of the flask. The reaction was allowed to slowly warm to room temperature, stirred overnight, and partitioned between saturated NH4Cl and EtOAc. The aqueous phase was extracted with EtOAc and the combined organic phases were dried over Na2SO4 and concentrated to give a yellow oil. The crude product was purified by flash chromatography using 40 g of silica gel and 0-50% of 9.5:0.5 MeOH:conc NH4OH in CH2Cl2 as eluant to afford 950 mg of impure 4-{hydroxy-[5-triisopropylsilanyl-2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-methyl}-4-methyl-piperidine-1-carboxylic acid tert-butyl ester. M+Na 691.

Workup

  1. temperatureto slowly warm to room temperature
  2. stirringstirred overnight
  3. custompartitioned between saturated NH4Cl and EtOAc
  4. extractionThe aqueous phase was extracted with EtOAc
  5. dry with materialthe combined organic phases were dried over Na2SO4
  6. concentrationconcentrated
  7. customto give a yellow oil
  8. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-ff67f7c072584fbe897183e351544853
Source dataset
uspto-grants-2011_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08008298B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes