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

HRID 658981Notes

Reaction equation

HRID 658981 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

7

Reactant 3

HCID 66111TrimethylsilylacetyleneHCID 81531DiisopropylethylamineHCID 59651823Methyl 1-(4-bromo-3-fluorobenzyl)azetidine-3-carboxylate

Product 1

HCID 59651825Methyl 1-(3-fluoro-4-(2-(trimethylsilyl)ethynyl)benzyl)azetidine-3-carboxylate

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Methyl 1-(4-bromo-3-fluorobenzyl)azetidine-3-carboxylate (25.00 g, 82.7 mmol), copper (I) 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) were combined in a sealable tube along with 100 mL THF. The tube was sealed and heated to 80 deg. C. under vigorous stirring for 24 h. The mixture was then cooled to room temperature, filtered, and evaporated. The resulting oil was purified by 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

  1. customThe tube was sealed
  2. temperatureheated to 80 deg. C
  3. filtrationfiltered
  4. customevaporated
  5. customThe resulting oil was purified by Biotage (75 L, 0-50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-c748c8dcc7644745a70c384d34e44329
Source dataset
uspto-grants-2011_12
Patent number
US08080542B2

Reaction notes

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