Water → 3-[(3R)-3-Hydroxypyrrolidin-1-yl]benzonitrile

HRID 2239333Notes

Reaction equation

HRID 2239333 reaction equation
F[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[C:5]#[N:6].[NH:10]1[CH2:14][CH2:13][C@@H:12]([OH:15])[CH2:11]1.O>CN1C(=O)N(C)CCC1>[OH:15][C@@H:12]1[CH2:13][CH2:14][N:10]([C:2]2[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=2)[C:5]#[N:6])[CH2:11]1

Participants

5

Reactant 3

HCID 962WaterHCID 678803-FluorobenzonitrileHCID 2759337(R)-3-Pyrrolidinol

Product 1

HCID 687092993-[(3R)-3-Hydroxypyrrolidin-1-yl]benzonitrileYield 63%

Reagents, catalysts & solvents 1

HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Conditions

Temperature
180 °C

Procedure

3-Fluorobenzonitrile (0.385 g, 3.18 mmol) and (3R)-pyrrolidin-3-ol (0.278 g, 3.19 mmol) were dissolved in DMPU (3 mL). The resulting mixture was subjected to microwave heating at 180° C. for 5 h. Water was added and the mixture extracted with ether. The organic layer washed with water, dried with MgSO4, filtered and concentrated. Purification on a 10 g Isolute Flash Si column (heptane/EtOAc 2:1→1:1) gave 0.375 g (63%) of the title compound. 1H NMR (400 MHz, MeOH-d4) δ 7.22 (dd, 1H, J=8.5, 7.5 Hz), 6.82 (d, 1H, J=7.5 Hz), 6.72 (dd, 1H, J=8.5, 2.2 Hz), 6.69 (bs, 1H), 4.48 (m, 1H), 3.42-3.33 (m, 2H), 3.24 (ddd, 1H, J=8.8, 8.8, 3.4 Hz), 3.13 (bd, 1H, J=10.5 Hz), 2.14-1.94 (m, 2H). 13C NMR (MeOH-d4) δ 149.2, 130.9, 120.6, 119.5, 117.0, 114.9, 113.4, 71.4, 56.7, 46.5, 34.7.

Workup

  1. extractionthe mixture extracted with ether
  2. washThe organic layer washed with water
  3. dry with materialdried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification on a 10 g Isolute Flash Si column (heptane/EtOAc 2:1→1:1)

Sources & evidence

ORD record
ord-3d0c1b7617ef4657bc544d1c1b7a0c3c
Source dataset
uspto-grants-2010_05
Patent number
US07723331B2

Reaction notes

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