Tetrahydrofuran → Ethyl 4-cyano-5-(2-(fluoromethyl)morpholino)-3-iodothiophene-2-carboxylate

HRID 2091677Notes

Reaction equation

HRID 2091677 reaction equation
[C:1]([C:3]1[C:4]([I:17])=[C:5]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[S:6][C:7]=1S(C)(=O)=O)#[N:2].Cl.[F:19][CH2:20][CH:21]1[O:26][CH2:25][CH2:24][NH:23][CH2:22]1.C1COCC1>>[C:1]([C:3]1[C:4]([I:17])=[C:5]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[S:6][C:7]=1[N:23]1[CH2:24][CH2:25][O:26][CH:21]([CH2:20][F:19])[CH2:22]1)#[N:2]

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 197772512-(Fluoromethyl)morpholine hydrochlorideHCID 40152062Ethyl 4-cyano-3-iodo-5-(methylsulfonyl)thiophene-2-carboxylate

Product 1

HCID 67072690Ethyl 4-cyano-5-(2-(fluoromethyl)morpholino)-3-iodothiophene-2-carboxylateYield 36.5%

Conditions

Temperature
90 °C

Procedure

A mixture of ethyl 4-cyano-3-iodo-5-(methylsulfonyl)thiophene-2-carboxylate (718 mg, 0.00186 mol), 2-(fluoromethyl)morpholine hydrochloride (348 mg, 0.00224 mol) and TEA (1.0 mL, 0.0072 mol) in THF (7.1 mL, 0.088 mol) was flushed with argon and then heated at 90° C. overnight. The reaction mixture was concentrated and purified by column chromatography to give ethyl 4-cyano-5-(2-(fluoromethyl)morpholino)-3-iodothiophene-2-carboxylate (288 mg, 36.4%). LCMS: (FA) ES+ 425, 1H NMR (400 MHz, d1-chloroform) δ: 4.57 (d, 1H), 4.46 (d, 1H), 4.34 (q, 2H), 4.12-4.05 (m, 1H), 4.02-3.77 (m, 4H), 3.34-3.25 (m, 1H), 3.22-3.14 (m, 1H), 1.37 (t, 3H).

Workup

  1. customwas flushed with argon
  2. concentrationThe reaction mixture was concentrated
  3. custompurified by column chromatography

Sources & evidence

ORD record
ord-62e77aed93824d38a8c88e22c73c5bd8
Source dataset
uspto-grants-2013_05
Patent number
US08440664B2

Reaction notes

Loading…