Triphenylphosphine → 3-[Isopropyl-(5-methyl-[1,3]dioxane-2-carbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester

HRID 73156Notes

Reaction equation

HRID 73156 reaction equation
[CH3:1][CH:2]1[CH2:7][O:6][CH:5]([C:8]([OH:10])=O)[O:4][CH2:3]1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C(=O)N(Cl)C(=O)C1.[CH3:38][O:39][C:40]([C:42]1[S:43][C:44]([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)=[CH:45][C:46]=1[NH:47][CH:48]([CH3:50])[CH3:49])=[O:41]>ClCCCl>[CH3:38][O:39][C:40]([C:42]1[S:43][C:44]([C:51]2[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=2)=[CH:45][C:46]=1[N:47]([CH:48]([CH3:50])[CH3:49])[C:8]([CH:5]1[O:4][CH2:3][CH:2]([CH3:1])[CH2:7][O:6]1)=[O:10])=[O:41]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 31398ChlorosuccinimideHCID 11737447Methyl 3-(isopropyl-amino)-5-phenylthiophene-2-carboxylateHCID 450846565-Methyl-1,3-dioxane-2-carboxylic acid

Product 1

HCID 597523643-[Isopropyl-(5-methyl-[1,3]dioxane-2-carbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl esterYield 35.7%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution 5-methyl-[1,3]dioxane-2-carboxylic acid (53 mg, 0.47 mmol) in 1,2-dichloroethane at 0° C. was treated with PPh3 (124 mg, 0.47 mmol), NCS (63 mg, 0.47 mmol) and isopropylamino-5-phenyl-thiophene-2-carboxylic acid methyl ester (100 mg, 0.36 mmol). The reaction was heated at reflux for 3 days. The mixture was evaporated to a residue that was purified by silica gel column chromatography using EtOAc:hexanes as eluent to furnished 3-[isopropyl-(5-methyl-[1,3]dioxane-2-carbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester (51.8 mg, 35% yield). 1H NMR (CDCl3, 400 MHz): 7.65 (d, 2H), 7.42 (m, 3H), 7.10 (s, 1H), 4.90 (q, 1H), 4.55 (s, 1H), 4.00 (dd, 1H), 3.90 (dd, 1H), 3.85 (s, 3H), 3.10 (t, 1H), 2.95 (t, 1H), 2.10 (m, 1H), 1.25 (d, 3H), 1.05 (d, 3H), 0.58 (d, 3H).

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 3 days
  3. customThe mixture was evaporated to a residue that
  4. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-5248748cce91411fab2930e589a97b32
Source dataset
uspto-grants-2014_09
Patent number
US08829030B2

Reaction notes

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