2-Methyl-3-butyn-2-ol → HCID 66869658, compound

HRID 333894Notes

Reaction equation

HRID 333894 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([N:10]2[CH2:15][CH2:14][C@:13]([CH2:22][C:23]([OH:26])([CH3:25])[CH3:24])([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[O:12][C:11]2=[O:27])[CH3:9])=[CH:4][CH:3]=1.[OH:28][C:29]([CH3:33])([CH3:32])[C:30]#[CH:31]>[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.CCN(CC)CC>[OH:26][C:23]([CH3:25])([CH3:24])[CH2:22][C@@:13]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[O:12][C:11](=[O:27])[N:10]([C@H:8]([C:5]2[CH:6]=[CH:7][C:2]([C:31]#[C:30][C:29]([OH:28])([CH3:33])[CH3:32])=[CH:3][CH:4]=2)[CH3:9])[CH2:15][CH2:14]1

Participants

6

Reactant 2

HCID 82582-Methyl-3-butyn-2-olHCID 44599033(S)-3-((S)-1-(4-bromophenyl)ethyl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one

Product 1

HCID 66869658HCID 66869658, compoundYield 89%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
100 °C

Procedure

A microwave vial was charged with (S)-3-((S)-1-(4-bromophenyl)ethyl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one (216 mg, 0.50 mmol), 3-hydroxy-3-methyl-1-butyne (0.24 mL, 2.50 mmol), CuI (9.5 mg, 0.05 mmol) and Et3N (4 mL). The mixture was sparged with N2 for 5 min and PdCl2(PPh3)2 (21 mg, 0.03 mmol) was added. The mixture was sparged with N2 for 5 min and heated at 100° C. for 2 h in the microwave. The mixture was diluted with EtOAc (200 mL), washed with 5% aq HCl (2×30 mL), satd aq NaHCO3 (30 mL) and brine (30 mL), and dried over Na2SO4. Removal of the solvent left a dark oil (379 mg) which was applied to a 2 g silica SPE Cartridge. The cartridge was eluted with 0, 25, 50 and 75% EtOAc in hexanes (20 mL) of each and EtOAc (2×20 mL) to give six fractions. Fractions 4 and 5 were pooled and concentrated to afford the title compound (193 mg, 89%) as an oil. LC-MS Method 1 tR=1.53 min, m/z=436, 378; 1H NMR (CDCl3) 1.12 (s, 3H), 1.18 (s, 3H), 1.52 (d, 3H), 1.60 (s, 6H), 2.15 (m, 1H), 2.19 (s, 2H), 2.20-2.45 (2H), 2.80 (m, 1H), 5.66 (q, 1H), 6.86 (d, 2H), 7.17 (d, 2H), 7.30-7.40 (5H)

Workup

  1. customThe mixture was sparged with N2 for 5 min
  2. customThe mixture was sparged with N2 for 5 min
  3. additionThe mixture was diluted with EtOAc (200 mL)
  4. washwashed with 5% aq HCl (2×30 mL)
  5. dry with materialdried over Na2SO4
  6. customRemoval of the solvent
  7. waitleft a dark oil (379 mg) which
  8. washThe cartridge was eluted with 0, 25, 50 and 75% EtOAc in hexanes (20 mL) of each and EtOAc (2×20 mL)
  9. customto give six fractions
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-f45c6197340f4ff4963fb1cd51e416e8
Source dataset
uspto-grants-2014_11
Patent number
US08883778B2

Reaction notes

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