Triethylamine → HCID 86652377, compound

HRID 2063713Notes

Reaction equation

HRID 2063713 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]2[CH2:19][CH2:18][CH2:17][C@H:16]2[CH2:20]C#N)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:30][S:31](Cl)(=[O:33])=[O:32].C(OCC)(=[O:37])C>C(Cl)Cl.O>[CH3:30][S:31]([O:33][CH2:20][C@@H:16]1[CH2:17][CH2:18][CH2:19][N:15]1[C:12]1[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:10][CH:11]=1)(=[O:37])=[O:32]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 31297Methanesulfonyl chlorideHCID 67085527HCID 67085527, compound

Product 1

HCID 86652377HCID 86652377, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

(S)-2-(1-(4-(benzyloxy)phenyl)pyrrolidin-2-yl)acetonitrile: To a clear, yellow homogeneous solution of 91A (14 g, 49.5 mmol) at 0° C. in methylene chloride (150 mL) was added triethylamine (13.3 mL, 98.9 mmol) and methanesulfonyl chloride (8.5 g, 74 mmol). The reaction mixture stirred at 0° C. becoming cloudy and orange in color. After 1 h, the reaction mixture was diluted with ethyl acetate and water. The combined organics were washed with 1N HCl, saturated sodium bicarbonate and brine, then were dried over MgSO4 and concentrated to yield (S)-(1-(4-(benzyloxy)phenyl)pyrrolidin-2-yl)methyl methanesulfonate (thick brown oil, 15 g, 41.5 mmol). To the solution of (S)-(1-(4-(benzyloxy)phenyl)pyrrolidin-2-yl)methyl methanesulfonate (15 g, 41.5 mmol) in DMSO (50 mL) was added sodium cyanide (6.1 g, 49 mmol) and the mixture was heated to 50° C. After 4 h, the reaction mixture was diluted with 1000 mL of ethyl acetate and 350 mL of water. The layers were extracted and the organic layer was washed twice with 200 mL of water, then 200 mL of brine. The organic layer was dried over MgSO4, filtered and evaporated to dryness to yield 15 g of an orange solid. The residue was purified silica gel column (60-120 mesh) with dichloromethane as eluent to yield 91B (off-white solid, 5 g, 34% yield). LC-MS Anal. Calc'd for C19H20N2O 292. found [M+H] 293.0. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.45 (5H, m), 6.91 (2H, d, J=8.80 Hz), 6.60 (2H, d, J=8.80 Hz), 5.03 (2H, s), 3.97 (1H, m), 3.42 (1H, m), 3.04 (1H, m), 2.71 (2H, m), 2.14 (2H, m), 1.9 (2H, m).

Workup

  1. washThe combined organics were washed with 1N HCl, saturated sodium bicarbonate and brine
  2. dry with materialwere dried over MgSO4
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-b30c86d601344a5e93b9ee6be78bc6b5
Source dataset
uspto-grants-2012_10
Patent number
US08288404B2

Reaction notes

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