Tetrahydrofuran → HCID 66748037, compound

HRID 2402168Notes

Reaction equation

HRID 2402168 reaction equation
Br[C:2]1[C:6]([Br:7])=[C:5]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[S:4][C:3]=1[C:14]([O:16][CH2:17][CH3:18])=[O:15].[Cl-].[Cl:20][C:21]1[CH:22]=[C:23]([CH:26]=[CH:27][C:28]=1[Cl:29])[CH2:24][Zn+].C1COCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:7][C:6]1[C:2]([CH2:24][C:23]2[CH:26]=[CH:27][C:28]([Cl:29])=[C:21]([Cl:20])[CH:22]=2)=[C:3]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[S:4][C:5]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1

Participants

5

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 66749408HCID 66749408, compoundHCID 178478123HCID 178478123, compound

Product 1

HCID 66748037HCID 66748037, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
95 °C

Procedure

A sealable reaction vessel containing a suspension of ethyl 3,4-dibromo-5-(morpholin-4-yl)thiophene-2-carboxylate (0.560 g, 1.40 mmol), 0.500 M 3,4-dichlorobenzylzinc chloride in THF (3.368 mL, 1.684 mmol) and THF (2.06 mL, 25.4 mmol) was purged via vacuum/backfilling with argon. To this suspension was added tetrakis(triphenylphosphine)palladium(0) (81.07 mg, 0.07016 mmol), the vial was capped, and the resulting black suspension was stirred at 95° C. overnight. The reaction mixture was adsorbed to celite in vacuo, and the solid thus obtained was purified via column chromatography (eluent: 0-15% EtOAc:hexane) to afford ethyl 4-bromo-3-(3,4-dichlorobenzyl)-5-(morpholin-4-yl)thiophene-2-carboxylate (323 mg, 50%). LCMS: (FA) ES+ 478, 480, 482; 1H NMR (400 MHz, DMSO) δ 7.53 (d, J=8.3 Hz, 1H), 7.39 (d, J=2.0 Hz, 1H), 7.07 (dd, J=8.3, 2.1 Hz, 1H), 4.36 (s, 2H), 4.22 (q, J=7.1 Hz, 2H), 3.75-3.70 (m, 4H), 3.17-3.12 (m, 4H), 1.22 (t, J=7.1 Hz, 3H).

Workup

  1. additionA sealable reaction vessel containing
  2. customwas purged via vacuum/backfilling with argon
  3. customthe vial was capped
  4. customthe solid thus obtained
  5. customwas purified via column chromatography (eluent: 0-15% EtOAc:hexane)

Sources & evidence

ORD record
ord-e0310aa76679429bb585523519243d43
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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