Boron trifluoride etherate → HCID 18188532, compound

HRID 1358130Notes

Reaction equation

HRID 1358130 reaction equation
[CH3:1][O:2][C:3]1[C:12]2[C:11]3[CH:13]=[CH:14][C:15]([CH2:17][S:18]([NH2:21])(=[O:20])=[O:19])=[CH:16][C:10]=3[CH:9](OC)[O:8][C:7]=2[CH:6]=[CH:5][CH:4]=1.B(F)(F)F.CCOCC.[Br-].[CH2:34]([O:36][C:37](=[O:41])[CH2:38][CH2:39][Zn+])[CH3:35].C([O-])(O)=O.[Na+]>ClCCl>[CH3:1][O:2][C:3]1[C:12]2[C:11]3[CH:13]=[CH:14][C:15]([CH2:17][S:18]([NH2:21])(=[O:19])=[O:20])=[CH:16][C:10]=3[CH:9]([CH2:39][CH2:38][C:37]([O:36][CH2:34][CH3:35])=[O:41])[O:8][C:7]=2[CH:6]=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 8000Boron trifluoride etherateHCID 516892Sodium BicarbonateHCID 18504036HCID 18504036, compoundHCID 178471816HCID 178471816, compound

Product 1

HCID 18188532HCID 18188532, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-10 °C

Procedure

A solution of the compound of Example 46A (33 mg, 0.1 mmol) in dichloromethane (10 mL) at −15° C. was treated dropwise with boron trifluoride etherate (38 μL, 0.3 mmol) and 3-ethoxy-3-oxopropylzinc bromide (660 μL, 0.33 mmol), warmed to −10° C. for 15 minutes and treated with saturated NaHCO3 (4 mL) to provide two layers. The layers were separated, and the aqueous layer was extracted with dichloromethane. The extract was dried (Na2SO4), filtered, and concentrated. The concentrate was purified by high throughput HPLC (0.1% TFA/MeCN gradient) to provide the desired product. MS (ESI(−)Q1MS) m/z 404 (M−H)−; 1H NMR (500 MHz, CD3OD) δ 1.23 (t, 3H, J=7.2 Hz), 1.99 (m, 1H), 2.09 (m, 1H), 2.49 (m, 2H), 2.99 (s, 3H), 3.92 (s, 3H), 4.10 (q, 2H, J=7.2 Hz), 5.04 (dd, 1H, J=9.4, 4.7 Hz), 6.59 (dd, 1H, J=8.1, 1.2 Hz), 6.72 (dd, 1H, J=8.5, 1.0 Hz), 7.08 (d, 1H, J=2.5 Hz), 7.15 (t, 1H, J=8.3 Hz), 7.20 (dd, 1H, J=8.8, 2.5 Hz), 8.36 (d, 1H, J=8.8 Hz).

Workup

  1. customto provide two layers
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with dichloromethane
  4. dry with materialThe extract was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe concentrate was purified by high throughput HPLC (0.1% TFA/MeCN gradient)

Sources & evidence

ORD record
ord-aff17e905ea041f0928f53b95ae98ba1
Source dataset
uspto-grants-2003_07
Patent number
US06593480B2

Reaction notes

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