Methanol → HCID 12137776, compound

HRID 841092Notes

Reaction equation

HRID 841092 reaction equation
[C:1]1([C:7]2[O:8][C:9]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[C:10]3[C:15]=2[CH:14]=[CH:13][CH:12]=[CH:11]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CO.[CH:24](=[O:28])/[CH:25]=[CH:26]/[CH3:27]>CN(C=O)C.O.CCOCC>[C:1]1([C@@:7]23[O:8][C@@:9]([C:16]4[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=4)([C@@H:25]([CH:24]=[O:28])[C@@H:26]2[CH3:27])[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:15]3=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 3

HCID 887MethanolHCID 216491,3-DiphenylisobenzofuranHCID 447466Crotonaldehyde

Product 1

HCID 12137776HCID 12137776, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

Conditions

Temperature
10 °C

Procedure

To a 10° C. solution of 5(13 mg, 0.058 mmol), 1,3-diphenylisobenzofuran (162 mg, 0.60 mmol), and MeOH (12 μL, 0.30 mmol) in DMF/H2O (95/5 v/v, 1.0 M) was added (E)-crotonaldehyde (25 μL, 0.30 mmol). The solution was stirred at 10° C. for 24 h. The reaction mixture was then diluted with Et2O (10 mL) and washed with H2O (10 mL). The aqueous layer was extracted with Et2O (10 mL×2) and the combined organics were dried (Na2SO4), and concentrated. Purification by silica gel chromatography (7% EtOAc/hex) afforded the title compound as a yellow solid in 75% yield (76 mg, 0.22 mmol); 35:1 exo:endo; 96% ee. Product ratios were determined, after reduction to the corresponding alcohol (4 eq NaBH4, EtOH (0.1 M)), by HPLC (Chiralcel OD-H column, 3% EtOAc/hex, 1.0 mL/min) exo isomers tr=14.1 min and 15.3 min, endo isomers tr=16.5 min and 20.8. IR (CH2Cl2) 3066, 3041, 2828, 2729, 1722, 1603, 1499, 1457, 1448, 1381, 1355, 1309 cm−1; 1H NMR (500 MHz, CDCl3) δ 9.36(d, J=5.8 Hz, 1H, CHO), 7.73-7.78(m, 2H, ArH), 7.43-7.57(m, 7H, ArH), 7.35-7.40(m, 1H, ArH), 7.16-7.26(m, 3H, ArH), 7.04-7.08(m, 1H, ArH), 3.08(dq, J=6.9, 4.1 Hz, 1H, CHCH3), 2.56(dd, J=5.8, 4.2 Hz, 1H, CHCHO), 0.96(d, J=6.9 Hz, 3H, CH3); 13C NMR (125 MHz) δ 201.9, 147.4, 145.0, 145.0, 136.6, 135.7, 135.5, 128.8, 128.6, 128.0, 127.4, 127.3, 127.0, 126.0, 125.5, 121.7, 118.5, 91.4, 89.2, 66.0, 43.0, 34.2, 30.3, 16.5; HRMS exact mass calcd for (C24H20O2) requires m/z 341.1541, found m/z 341.1542; [α]D=−82.4(c=1.0, CHCl3).

Workup

  1. washwashed with H2O (10 mL)
  2. extractionThe aqueous layer was extracted with Et2O (10 mL×2)
  3. dry with materialthe combined organics were dried (Na2SO4)
  4. concentrationconcentrated
  5. customPurification by silica gel chromatography (7% EtOAc/hex)

Sources & evidence

ORD record
ord-a2685e83fafb43598c6ed3a609b6cc10
Source dataset
uspto-grants-2002_04
Patent number
US06369243B1

Reaction notes

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