Formic Acid → Z-(2S,3R)-3-(1-tert-Butoxycarbonyl-3-hydroxy-2-phenylpiperidin-3-yl)-2-(2-methoxyphenyl)prop-2-en-1-ol

HRID 1420823Notes

Reaction equation

HRID 1420823 reaction equation
C(O)=O.[C:4]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH2:14][C@:13]([C:18]#[C:19][CH2:20][OH:21])([OH:17])[C@@H:12]1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:10])([CH3:7])([CH3:6])[CH3:5].C1(C)C=CC=CC=1P.C(N(CCCC)CCCC)CCC.I[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][C:51]=1[O:56][CH3:57]>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:4]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH2:14][C@:13](/[CH:18]=[C:19](/[C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][C:51]=2[O:56][CH3:57])\[CH2:20][OH:21])([OH:17])[C@@H:12]1[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)=[O:10])([CH3:7])([CH3:5])[CH3:6]

Participants

8

Reactant 5

HCID 284Formic AcidHCID 7622TributylamineHCID 68257o-IodoanisoleHCID 11301992(2S,3R)-1-tert-Butoxycarbonyl-3-(3-hydroxypropyn-1-yl)-2-phenylpiperidin-3-olHCID 15049146(2-Methylphenyl)phosphane

Product 1

HCID 70290294Z-(2S,3R)-3-(1-tert-Butoxycarbonyl-3-hydroxy-2-phenylpiperidin-3-yl)-2-(2-methoxyphenyl)prop-2-en-1-olYield 35%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

Formic acid (138 ml, 3.77 mmol) was added to a stirred, degassed solution of (2S,3R)-1-tert-butoxycarbonyl-3-(3-hydroxypropyn-1-yl)-2-phenylpiperidin-3-ol (Description 7, 473 mg, 1.43 mmol), palladium (II) acetate (33 mg, 0.14 mmol), trio-o-tolylphosphine (85 mg, 0.28 mmol), tributylamine (1.12 ml, 4.87 mmol) and 2-iodoanisole (446 ml, 3.44 mmol) in N,N-dimethylformamide (3 ml) at room temperature and the resulting mixture was heated at 70° C. for 5 h. The mixture was cooled, filtered, diluted with ethyl acetate (50 ml), washed with water (100 ml), hydrochloric acid (2M, 50 ml) and saturated aqueous sodium chloride (50 ml), dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was chromatographed on silica gel, eluting with hexane/ethyl acetate (60:40) to give the title compound as a yellow glass (220 mg, 35%). 1H NMR (360 MHz, CDCl3) δ7.41 (2H, d, J 7.6 Hz), 7.22-7.34 (4H, m), 7.12 (1H, dd, J 1.7, 7.4 Hz), 6.94 (1H, t, J 7.5 Hz), 6.89 (1H, d, J 8.2 Hz), 5.84 (1H, s), 5.00 (1H, s), 4.40 (1H, d, J 12.7 Hz), 4.15 (1H, dd, J 6.0, 13.1 Hz), 4.05 (1H, d, J 12.5 Hz), 3.86 (3H, s), 3.44 (1H, dt, J 5.6, 12.3 Hz), 2.04-2.18 (1H, m), 1.80-1.96 (3H, m), 1.28 (9H, s), and 1.64-1.84 (3H, m). m/z (ES+) 440 (M+1).

Workup

  1. temperatureThe mixture was cooled
  2. filtrationfiltered
  3. additiondiluted with ethyl acetate (50 ml)
  4. washwashed with water (100 ml), hydrochloric acid (2M, 50 ml) and saturated aqueous sodium chloride (50 ml)
  5. dry with materialdried (MgSO4)
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was chromatographed on silica gel
  8. washeluting with hexane/ethyl acetate (60:40)

Sources & evidence

ORD record
ord-0bfc2d47ee8245d6b538ef863afd1c1a
Source dataset
uspto-grants-2000_06
Patent number
US06071927

Reaction notes

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