Ethanol → HCID 178445756, compound

HRID 2389044Notes

Reaction equation

HRID 2389044 reaction equation
[NH2:1][C@@:2]([C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[C:11]([O:16][CH:17]3[CH2:22][CH2:21][CH:20]([CH2:23][CH2:24][CH2:25][CH3:26])[CH2:19][CH2:18]3)[CH:12]=2)[CH:7]=1)([CH3:5])[CH2:3][OH:4].[OH-].[Li+].C(O)C.O>>[NH2:1][C@@:2]([C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[C:11]([O:16][C@H:17]3[CH2:18][CH2:19][C@H:20]([CH2:23][CH2:24][CH2:25][CH3:26])[CH2:21][CH2:22]3)[CH:12]=2)[CH:7]=1)([CH3:5])[CH2:3][OH:4]

Participants

5

Reactant 4

HCID 702EthanolHCID 962WaterHCID 3939Lithium HydroxideHCID 46196153HCID 46196153, compound

Product 1

HCID 178445756HCID 178445756, compoundYield 66%

Procedure

The mixture of carbamate (Example 7; 360 mg 0.00094 mol, cis and trans mixture) and lithium hydroxide (248 mg, 0.0104 mol) in ethanol (6.0 mL, 0.10 mol) and water (2.0 mL, 0.11 mol) was heated to reflux for overnight. LCMS showed reaction completed. The solvent was removed under vacuum and the residue was partitioned between water/CH2Cl2. The aqueous layer was extensively extracted with CH2Cl2. The combined organic phase was dried over Na2SO4. The concentrated residue was taken up into DCM and subjected to chromatographic purification with CH2Cl2/MeOH (10:90 to 80:20) to give the product (220 mg, 66%). Separation on ChiralPak-ADH (5μ, 4.6 mm×250 mm, 2 mL/min, 25% (0.3% DEA in MeOH) in CO2, 100 bar, 36° C.) gave peak 1, Rf=8.373 min, 87 mg (87.9% yield, 96.4% ee), and peak 2, Rf=12.479 min, 74 mg (74.7% yield, 97.0% ee). Peak 1 was purified on Si gel (0-100% MeOH/DCM) to give 26.2 mg; peak 2 was purified on Si gel (0-100% MeOH/DCM) to give 44.3 mg. LCMS 339.71 ([M-NH2]+, 100%). 1H NMR (400 MHz, CD3OD) δ ppm 0.93 (t, J=6.9 Hz, 3H), 1.14 (ddd, J=14.7, 13.4, 3.0 Hz, 2H), 1.24-1.39 (m, 7H), 1.45 (ddd, J=14.7, 12.5, 3.3 Hz, 2H), 1.56 (s, 3H), 1.89 (br d, J=13.0 Hz, 2H), 2.22 (brd, J=12.5 Hz, 2 H), 3.70 (d, J=10.9 Hz, 1H), 3.76 (d, J=10.9 Hz, 1H), 4.37 (m, 1H), 7.11 (dd, J=9.0, 2.6 Hz, 1H), 7.21 (d, J=2.5 Hz, 1H), 7.55 (dd, J=8.7, 2.0 Hz, 1H), 7.74 (d, J=6.6 Hz, 1H), 7.76 (d, J=6.9 Hz, 1H), 7.84 (d, J=1.9 Hz, 1H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for overnight
  3. customreaction
  4. customThe solvent was removed under vacuum
  5. customthe residue was partitioned between water/CH2Cl2
  6. extractionThe aqueous layer was extensively extracted with CH2Cl2
  7. dry with materialThe combined organic phase was dried over Na2SO4
  8. customsubjected to chromatographic purification with CH2Cl2/MeOH (10:90 to 80:20)

Sources & evidence

ORD record
ord-881232add6a54b6fa06bad667cebf337
Source dataset
uspto-grants-2012_09
Patent number
US08269043B2

Reaction notes

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