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Triethylamine → 3-(1-Boc-2-(r)-azetidinylmethoxy)-6-chloro-5-(trimethylsilylethynyl)pyridine

HRID 365915
Notes
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Reaction equation

HRID 365915 reaction equation
[C:1]([N:8]1[CH2:11][CH2:10][C@@H:9]1[CH2:12][O:13][C:14]1[CH:15]=[N:16][C:17]([Cl:21])=[C:18](Br)[CH:19]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CCN(CC)CC.[CH3:29][Si:30]([C:33]#[CH:34])([CH3:32])[CH3:31]>C1(C)C=CC=CC=1.[I+].[Cu+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([N:8]1[CH2:11][CH2:10][C@@H:9]1[CH2:12][O:13][C:14]1[CH:15]=[N:16][C:17]([Cl:21])=[C:18]([C:34]#[C:33][Si:30]([CH3:32])([CH3:31])[CH3:29])[CH:19]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 229618073-(1-Boc-2-(r)-azetidinylmethoxy)-5-bromo-6-chloropyridine

Product 1

HCID 229618103-(1-Boc-2-(r)-azetidinylmethoxy)-6-chloro-5-(trimethylsilylethynyl)pyridineYield 62.2%

Reagents, catalysts & solvents 3

HCID 178418397
HCID 178418397, compound
Catalyst
HCID 178505377HCID 178505377, compoundCatalyst
HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 3-(1-BOC-2-(R)-azetidinylmethoxy)-6-chloro-5-bromopyridine (660 mg, 1.75 mmol) in toluene (20 mL) was added NEt3 (0.7 mL), copper (I) iodine (33 mg), tetrakis(triphenylphosphine)palladium (0) (201 mg) and (trimethylsilyl)acetylene (0.30 mL, 2.10 mmol). The reaction mixture was stirred and heated at 100° C. for 16 h. Solvent was evaporated and the residue was chromatographed (silica gel; hexane/EtoAc, 5:1 to 2:1) to afford an oil (430 mg, 62%): 1H NMR (CDCl3, 300 MHz) δ 1.42 (s, 9H), 2.20-2.40 (m, 2H), 3.80-3.92 (m, 2H), 4.10 (m, 1H), 4.30 (m,1H), 4.50 (m, 1H), 7.37 (d, (H, J=3.0 Hz), 8.05 (d, 1H, J=3.0 Hz); MS (CI/NH3) m/z 395 (M+H)+.

Workup

  1. customSolvent was evaporated
  2. customthe residue was chromatographed (silica gel; hexane/EtoAc, 5:1 to 2:1)

Sources & evidence

ORD record
ord-0d484c2eeb0f41ee9ddffa78538276ef
Source dataset
uspto-grants-2000_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US06127386

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes