Tri-o-tolylphosphine → HCID 178448164, compound

HRID 2285395Notes

Reaction equation

HRID 2285395 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([C@H:12]([OH:14])[CH3:13])=[CH:9]2)=[CH:4][CH:3]=1.[C:15]([SiH2:19][O:20][C:21]([CH3:38])([CH3:37])[C@@:22]([CH3:36])([CH:34]=[CH2:35])[C:23]([N:25]1[C@H:29]([CH:30]([CH3:32])[CH3:31])[CH2:28][O:27][C:26]1=[O:33])=[O:24])([CH3:18])([CH3:17])[CH3:16].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C1(CNCC2CCCCC2)CCCCC1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:15]([SiH2:19][O:20][C:21]([CH3:37])([CH3:38])[C@@:22]([CH3:36])(/[CH:34]=[CH:35]/[C:2]1[CH:3]=[CH:4][C:5]2[C:10](=[CH:9][C:8]([C@H:12]([OH:14])[CH3:13])=[CH:7][CH:6]=2)[CH:11]=1)[C:23]([N:25]1[C@H:29]([CH:30]([CH3:31])[CH3:32])[CH2:28][O:27][C:26]1=[O:33])=[O:24])([CH3:18])([CH3:17])[CH3:16]

Participants

7

Reactant 4

HCID 80271Tri-o-tolylphosphine2×HCID 4594378Bis(cyclohexylmethyl)amineHCID 86709687HCID 86709687, compoundHCID 131733540HCID 131733540, compound

Product 1

HCID 178448164HCID 178448164, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalyst2×HCID 312751,4-DioxaneSolvent

Procedure

A solution of (R)-1-(7-bromo-naphthalen-2-yl)-ethanol (121.5 mg, 0.484 mmol), (R)-3-[(R)-2-(tert-butyl-dimethyl-silanyloxymethyl)-2-methyl-but-3-enoyl]-4-isopropyl-oxazolidin-2-one (172.0 mg, 0.484 mmol), palladium(II)acetate (22 mg, 0.097 mmol), tri(o-tolyl)phosphine (29.5 mg, 0.097 mmol) and N,N-dicylohexylmethylamine (0.26 mL, 1.210 mmol) in anhydrous 1,4-dioxane (10 mL) was heated at reflux for 1.5 h. The mixture was treated with palladium(II) acetate (22 mg, 0.097 mmol) and tri(o-tolyl)phosphine (29.5 mg, 0.097 mmol). After stirring at reflux for 24 h and cooling to warm temperature the reaction was quenched with hydrochloric acid (1 M, 20 mL). The aqueous layer was extracted with ethyl acetate. The combined organics were washed with a saturated solution of sodium bicarbonate dried over anhydrous sodium sulfate, filtered and the volatiles were removed in vacuo. The residue was purified by silica gel chromatography using a 25 g Isolute cartridge eluted with a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 4:1 to afford the title compound (116.7 mg, 46%) as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 0.07 (s, 6H), 0.91 (s, 9H), 1.15-1.30 (m, 6H), 1.55-1.65 (m, 6H), 2.29-2.46 (m, 1H), 3.83 (d, J=9.6 Hz, 1H), 4.10-4.33 (m, 2H), 4.50-4.60 (m, 2H), 5.00-5.15 (m, 1H), 6.47 (d, J=16.5 Hz, 1H), 6.70 (d, J=16.5 Hz, 1H), 7.11-7.22 (m, 2H), 7.40-7.50 (m, 2H), 7.72-7.82 (m, 2H). LCMS (m/z) 526.3 [M+H], Tr=4.03 min.

Workup

  1. temperatureat reflux for 1.5 h
  2. temperatureat reflux for 24 h
  3. temperaturecooling
  4. temperatureto warm temperature the reaction
  5. customwas quenched with hydrochloric acid (1 M, 20 mL)
  6. extractionThe aqueous layer was extracted with ethyl acetate
  7. washThe combined organics were washed with a saturated solution of sodium bicarbonate
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. customthe volatiles were removed in vacuo
  11. customThe residue was purified by silica gel chromatography
  12. washeluted with a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 4:1

Sources & evidence

ORD record
ord-e7a2f6a30c5744c3b807d0d99994a2ef
Source dataset
uspto-grants-2015_09
Patent number
US09145441B2

Reaction notes

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