Formic Acid → HCID 90406331, compound

HRID 2277040Notes

Reaction equation

HRID 2277040 reaction equation
CCN(CC)CC.C(O)=O.[O:11]=[C:12]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH2:23][CH:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[CH:17]=1)[CH2:13][C:14]#[N:15]>CCOC(C)=O.O>[OH:11][C@@H:12]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH2:23][CH:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[CH:17]=1)[CH2:13][C:14]#[N:15]

Participants

6

Reactant 3

HCID 284Formic AcidHCID 8471TriethylamineHCID 90406336HCID 90406336, compound

Product 1

HCID 90406331HCID 90406331, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

The solution of Et3N (0.78 g, 7.6 mmol) in EtOAc (50 mL) was cooled to 0° C. for 15 min. HCOOH (0.88 g, 19 mmol) was added dropwise to the reaction mixture and the solution was stirred for 20 min at same temperature. The solution of 0.2 mol % (R,R)RuCl-TsDPEN(p-cymene) (10 mg) in EtOAc was added to the reaction mixture, followed by addition of ketonitrile (13) (1.0 g, 3.8 mmol) in EtOAc at 0° C. The reaction mixture was stirred for 18 h at rt. After completion of the reaction (as monitored by TLC) the reaction mixture was diluted with water, extracted with EtOAc, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Purification by column chromatography (100-200 silica mesh, 20-25% EtOAc in hexanes) gave (R)-3-hydroxy-3-(3-((tetrahydro-2H-pyran-4-yl)methoxy)phenyl)propanenitrile (14) as a white solid. Yield (0.75 g, 75%); 1H NMR (400 MHz, DMSO-d6) δ 7.24 (t, J=8.0 Hz, 1H), 6.98-6.95 (m, 2H), 6.83 (dd, J=8.0, 4.0 Hz, 1H), 5.92 (d, J=4.8 Hz, 1H), 4.85 (dd, J=11.2, 4.8 Hz, 1H), 3.89-3.81 (m, 4H), 3.35-3.30 (m, 2H), 2.84 (dq, J=16.8, 4.8 Hz, 2H), 2.04-1.96 (m, 1H), 1.69-1.66 (m, 2H), 1.37-1.27 (m, 2H).

Workup

  1. stirringThe reaction mixture was stirred for 18 h at rt
  2. customAfter completion of the reaction (as monitored by TLC) the reaction mixture
  3. extractionextracted with EtOAc
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customPurification by column chromatography (100-200 silica mesh, 20-25% EtOAc in hexanes)

Sources & evidence

ORD record
ord-25f00259b1dc47cb8fd70ccbffe67a9d
Source dataset
uspto-grants-2015_09
Patent number
US09133154B2

Reaction notes

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