HCID 86709201, compound → HCID 86709200, compound

HRID 1851142Notes

Reaction equation

HRID 1851142 reaction equation
[CH2:1]([N:8]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C@H:9]([CH3:16])[C:10](=[O:15])[C:11]([F:14])([F:13])[F:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:24][Mg]I>CCOCC>[CH2:17]([N:8]([CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C@H:9]([CH3:16])[C@:10]([CH3:24])([OH:15])[C:11]([F:14])([F:12])[F:13])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

4

Reactant 2

HCID 86709201HCID 86709201, compoundHCID 178418373HCID 178418373, compound

Product 1

HCID 86709200HCID 86709200, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

(R)-3-(Dibenzylamino)-1,1,1-trifluorobutan-2-one (Example 52A) (3.41 g, 10.61 mmol) was dissolved in Et2O (80 mL) and then cooled to ca. 0° C. (ice external temp) prior to the addition of MeMgI (7.07 mL, 3 M). Addition of the Grignard reagent caused the reaction to become heterogeneous. After stirring for 10 min, TLC indicated good conversion to a slightly less polar than sm product (a trace of what appeared to be sm remained), the mixture was quenched with sat. aq. NH4Cl and extracted with EtOAc. The combined organic portions were dried over Na2SO4 and concentrated. The resulting bright yellow residue was purified by flash chromatography (ISCO, 80 g silica, 0% to 40% over 27 min. ca. 10 min ret time; hex/EtOAc) to afford the desired product as a bright yellow oil. TLC, LCMS, and NMR showed ca.15-20% of the bis CF3 alcohol contaminating the desired product. A trace of the other diastereomer also existed. The material was concentrated and rechromatographed (straight CH2Cl2, 80 g SiO2, 254/230 nm) to afford separation of the bis-CF3 alcohol and desired product (1.94 g, 54%). This material was used in its entirety for the debenzylation step: 1H NMR (400 MHz, DMSO-d6) δ 7.62-7.48 (m, 10H), 6.11 (s, 1H), 4.16 (d, J=13.6 Hz, 2H), 3.61 (d, J=13.7 Hz, 2H), 3.15 (q, J=6.8 Hz, 1H), 1.42-1.40 (m, 6H).

Workup

  1. customthe reaction
  2. customwas quenched with sat. aq. NH4Cl
  3. extractionextracted with EtOAc
  4. dry with materialThe combined organic portions were dried over Na2SO4
  5. concentrationconcentrated
  6. customThe resulting bright yellow residue was purified by flash chromatography (ISCO, 80 g silica, 0% to 40% over 27 min. ca. 10 min ret time; hex/EtOAc)

Sources & evidence

ORD record
ord-3589969c82ba46c1ab788af842d8b72b
Source dataset
uspto-grants-2015_02
Patent number
US08957104B2

Reaction notes

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