Methyl 5-bromothiophene-2-carboxylate → HCID 20779309, compound

HRID 2179929Notes

Reaction equation

HRID 2179929 reaction equation
[CH3:1][O:2][C:3](=[O:47])[CH:4]([N:12]([S:33]([C:36]1[C:41]([CH3:42])=[CH:40][C:39]([O:43][CH3:44])=[C:38]([CH3:45])[C:37]=1[CH3:46])(=[O:35])=[O:34])[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([Sn](CCCC)(CCCC)CCCC)=[CH:16][CH:15]=1)[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[CH3:48][O:49][C:50]([C:52]1[S:53][C:54](Br)=[CH:55][CH:56]=1)=[O:51]>C1(C)C=CC=CC=1>[CH3:48][O:49][C:50]([C:52]1[S:53][C:54]([C:17]2[CH:18]=[CH:19][C:14]([CH2:13][N:12]([CH:4]([C:3]([O:2][CH3:1])=[O:47])[CH2:5][C:6]3[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=3)[S:33]([C:36]3[C:41]([CH3:42])=[CH:40][C:39]([O:43][CH3:44])=[C:38]([CH3:45])[C:37]=3[CH3:46])(=[O:35])=[O:34])=[CH:15][CH:16]=2)=[CH:55][CH:56]=1)=[O:51]

Participants

4

Reactant 2

HCID 605713Methyl 5-bromothiophene-2-carboxylateHCID 86590426HCID 86590426, compound

Product 1

HCID 20779309HCID 20779309, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a stirred solution of 2-[(4-Methoxy-2,3,6-trimethyl-benzenesulfonyl)-(4-tributylstannanyl-benzyl)-amino]-3-phenyl-propionic acid methyl ester (100 mg. 0.13 mmol.) in toluene (3 ml.) were added P(Ph3)4Pd (6 mg. 0.039eq.), CuBr (2 mg.) and 5-Bromo-thiophene-2-carboxylic acid methyl ester (26.5 mg, 0.12 mmol.) under nitrogen. The reaction mixture was stirred and heated to reflux during 5 hrs. The progress of the reaction was monitored by TLC. Filtration and removal of the solvent under reduced pressure on a rotary evaporator followed by silica plate for purification using 80% hexane 20% EtOAc afforded 5-(4-{[(1-Methoxycarbonyl-2-phenyl-ethyl)-(4-methoxy-2,3,6-trimethyl-benzenesulfonyl)-amino]-methyl}-phenyl)-thiophene-2-carboxylic acid methyl ester in 41% yield: 1HNMR (Varian 400 MHz, CDCl3) δ8.67(d, 1H, HPh), 8.35 (d, 2H, thiopheneH), 8.10(m, 6H, HPh), 8.00(d, 2H, thiopheneH), 7.38(s, 1H, MTRH), 5.72(m, 3H, NCH2Ph, CHCH2), 4.82(s, 3H, OCH3), 4.68(s, 3H, COOCH3), 4.29(s, 3H, COOCH3), 4.10 (m, 1H, CHCH2), 3.85 (m, 1H, CHCH2), 3.57(s, 3H, ArCH3), 3.40(s, 3H, ArCH3), 3.0(s, 3H, ArCH3) ppm. MS 622.6 (M+).

Workup

  1. temperatureheated
  2. temperatureto reflux during 5 hrs
  3. filtrationFiltration and removal of the solvent under reduced pressure
  4. customon a rotary evaporator
  5. customfollowed by silica plate for purification

Sources & evidence

ORD record
ord-62e61325f7094c13a1dea6f95fc0be74
Source dataset
uspto-grants-2005_05
Patent number
US06887877B2

Reaction notes

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