Methanol → HCID 44604051, compound

HRID 713677Notes

Reaction equation

HRID 713677 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[C:5]([CH:11]=[CH:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)[C:4]=1[CH:21]([C:23]1[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=[C:25]([O:31][CH3:32])[CH:24]=1)O.C(O)(C(F)(F)F)=[O:34].C([O-])([O-])=O.[K+].[K+].CO>C(Cl)Cl.O>[CH3:32][O:31][C:25]1[CH:24]=[C:23]([CH:21]2[C:4]3[C:5](=[CH:6][C:7]([O:9][CH3:10])=[CH:8][C:3]=3[O:2][CH3:1])[CH:11]([OH:34])[CH:12]2[C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 90702066HCID 90702066, compound

Product 1

HCID 44604051HCID 44604051, compoundYield 75.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-20 °C

Procedure

To a solution of aldol adduct 11 (0.150 g, 0.344 mmol, 1.0 equiv) in CH2Cl2 (10 mL) at −78° C. was added in a single portion a solution of TFA (0.027 mL, 0.344 mmol, 1.0 equiv) in CH2Cl2 (0.2 mL). The resultant dark purple reaction mixture was then warmed slowly to −20° C. over the course of 30 min and stirred for 5 h at −20° C. Upon completion, the reaction mixture was quenched sequentially with solid K2CO3 (0.475 g, 3.44 mmol, 10 equiv) and MeOH (10 mL), warmed to 25° C., and stirred for 15 min at 25° C. The reaction contents were then poured into water (15 mL) and extracted with EtOAc (3×40 mL). The combined organic layers were washed with water (15 mL) and brine (15 mL), dried (MgSO4), and concentrated. The resultant brown oil was purified by flash column chromatography (silica gel, EtOAc/hexanes, 2:1) to give alcohol 15 (0.113 g, 75% yield) as an amorphous white solid. 15: Rf=0.41 (silica gel, EtOAc/hexanes, 1:1); IR (film) νmax 2935, 1597, 1512, 1463, 1304, 1248, 1203, 1151, 1060, 829; 1H NMR (300 MHz, CDCl3) δ 7.09 (d, J=8.7 Hz, 2H), 6.83 (d, J=8.7 Hz, 2H), 6.65 (d, J=2.1 Hz, 1H), 6.42 (d, J=2.1 Hz, 1H), 6.27 (t, J=2.3 Hz, 1H), 6.17 (d, J=2.4 Hz, 2H), 5.13 (app t, J=5.7 Hz, 1H), 4.19 (d, J=6.9 Hz, 1H), 3.86 (s, 3H), 3.79 (s, 3H), 3.68 (s, 3H), 3.59 (s, 3H), 3.18 (d, J=6.6 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 161.7, 160.4, 158.5, 157.1, 146.9, 146.3, 134.0, 128.7, 122.9, 113.9, 105.5, 99.7, 99.4, 99.3, 98.0, 82.5, 66.1, 55.6, 55.3, 55.2, 54.7; HRMS (MALDI-FTMS) calculated for C26H21O6+ [M+] 436.1886. found 436.1870.

Workup

  1. temperaturewarmed to 25° C.
  2. stirringstirred for 15 min at 25° C
  3. customThe reaction contents
  4. extractionextracted with EtOAc (3×40 mL)
  5. washThe combined organic layers were washed with water (15 mL) and brine (15 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customThe resultant brown oil was purified by flash column chromatography (silica gel, EtOAc/hexanes, 2:1)

Sources & evidence

ORD record
ord-2698f6212b944b17a8fdec5a3dda5221
Source dataset
uspto-grants-2015_11
Patent number
US09185909B2

Reaction notes

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