Trimethylsilylacetylene → Methyl 1-(3-fluoro-4-(2-(trimethylsilyl)ethynyl)benzyl)azetidine-3-carboxylate

HRID 2075183Notes

Reaction equation

Br[C:2]1[CH:16]=[CH:15][C:5]([CH2:6][N:7]2[CH2:10][CH:9]([C:11]([O:13][CH3:14])=[O:12])[CH2:8]2)=[CH:4][C:3]=1[F:17].[CH3:18][Si:19]([C:22]#[CH:23])([CH3:21])[CH3:20].CCN(C(C)C)C(C)C>[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1>[F:17][C:3]1[CH:4]=[C:5]([CH:15]=[CH:16][C:2]=1[C:23]#[C:22][Si:19]([CH3:21])([CH3:20])[CH3:18])[CH2:6][N:7]1[CH2:10][CH:9]([C:11]([O:13][CH3:14])=[O:12])[CH2:8]1

Participants

Conditions

Temperature: 80 °C

Procedure

Methyl 1-(4-bromo-3-fluorobenzyl)azetidine-3-carboxylate (25.00 g, 82.7 mmol), copper (1) iodide (3.14 g, 16.5 mmol), (trimethylsilyl)acetylene (81.9 mL, 579 mmol), bis(triphenylphosphine)palladium(ii) chloride (5.81 g, 8.27 mmol), and Hunig's base (115 mL, 662 mmol) was added in a sealable tube along with 100 mL THF. The reaction is sealed and heated to 80° C. under vigorous stirring for 24 h. The mixture was cooled to room temperature, filtered and evaporated. The resulting oil was purified using Biotage (75 L, 0-50% EtOAc/hexanes) affording methyl 1-(3-fluoro-4-(2-(trimethylsilyl)ethynyl)benzyl)azetidine-3-carboxylate as a transparent brown oil. MS (ESI) m/z: Calculated: 319.1; Observed: 320.1 (M++1).

Workup

customThe reaction is sealed
temperatureThe mixture was cooled to room temperature
filtrationfiltered
customevaporated
customThe resulting oil was purified

Sources & evidence

ORD record: ord-39176ca7115347979717ca6166901ed8
Source dataset: uspto-grants-2011_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07919519B2

Reaction notes

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