Acetonitrile → (2S)-3-(2-(3-chlorophenyl)morpholino)-1,1,1-trifluoropropan-2-ol

HRID 530599Notes

Reaction equation

HRID 530599 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]([CH:9]2[O:14][CH2:13][CH2:12][NH:11][CH2:10]2)[CH:6]=[CH:7][CH:8]=1.CCN(C(C)C)C(C)C.C(#N)C.[F:27][C:28]([F:33])([F:32])[C@@H:29]1[CH2:31][O:30]1>O>[Cl:2][C:3]1[CH:4]=[C:5]([CH:9]2[CH2:10][N:11]([CH2:31][C@H:29]([OH:30])[C:28]([F:33])([F:32])[F:27])[CH2:12][CH2:13][O:14]2)[CH:6]=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 81531DiisopropylethylamineHCID 7171781(2S)-2-(Trifluoromethyl)oxiraneHCID 1178699012-(3-Chlorophenyl)morpholine hydrochloride

Product 1

HCID 118276730(2S)-3-(2-(3-chlorophenyl)morpholino)-1,1,1-trifluoropropan-2-olYield 82.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

In a 50 mL round-bottomed flask, 2-(3-chlorophenyl)morpholine hydrochloride (OChem., Lot #100301A1, 200 mg, 854 μmol) and DIEA (265 mg, 358 μl, 2.05 mmol) were combined with acetonitrile (2.5 ml) to give an off-white suspension. (S)-2-(trifluoromethyl)oxirane (287 mg, 2.56 mmol) was added. The reaction mixture was stirred at room temperature for 48 h. Reaction was complete by LCMS (MH+=310). The reaction mixture was poured into 50 mL H2O and extracted with diethyl ether/dichloromethane 10:1 (3×50 mL). The organic layers were combined, washed with saturated NaCl (1×50 mL), dried over MgSO4 and concentrated in vacuo to afford 218 mg (82% yield) of (2S)-3-(2-(3-chlorophenyl)morpholino)-1,1,1-trifluoropropan-2-ol as an amber oil. (MH+=310).

Workup

  1. customto give an off-white suspension
  2. customReaction
  3. extractionextracted with diethyl ether/dichloromethane 10:1 (3×50 mL)
  4. washwashed with saturated NaCl (1×50 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-09bc7081625940c5a417ed9d2ceec003
Source dataset
uspto-grants-2016_05
Patent number
US09353096B2

Reaction notes

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