Hydrochloric Acid → HCID 14452371, compound

HRID 641620Notes

Reaction equation

HRID 641620 reaction equation
Br[C:2]1[S:3][CH:4]=[CH:5][C:6]=1[NH:7][C:8](=O)OC(C)(C)C.C([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1B(O)O)=O.C(=O)(O)[O-].[Na+].Cl.[OH-].[Na+]>C(COC)OC.C(Cl)Cl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[S:3]1[C:2]2[C:22]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[CH:8]=[N:7][C:6]=2[CH:5]=[CH:4]1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 2921892-Formylphenylboronic acidHCID 516892Sodium BicarbonateHCID 13164363tert-Butyl (2-bromothiophen-3-yl)carbamate

Product 1

HCID 14452371HCID 14452371, compoundYield 83%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
23 °C

Procedure

Tert-butyl 2-bromothien-3-ylcarbamate (35 g, 0.13 mol), 2-Formylphenylboronic acid (Cmpd IIIa, 25 g, 0.17 mol), [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium [II] (5.3 g, 6.5 mmol), and sodium bicarbonate (33 g, 0.39 mol) were combined in 40% aqueous dimethoxyethane (675 mL) and the mixture was heated to reflux. After 1 h the mixture was cooled to 23° C., treated slowly with 2 N aqueous hydrochloric acid (405 mL) and heated back to reflux for an additional 2 h. At this time the mixture was cooled to 23° C., treated slowly with 2.5 N aqueous sodium hydroxide (270 mL) and stirred for ca. 15 min. The mixture was filtered through Celite and washed with ethyl acetate (2.2 L). The organic layer was separated from the filtrate and washed with water and brine (2.2 L each), dried (K2CO3), and concentrated in vacuo to give the crude product (28 g) as a dark oil. The oil was taken up in methylene chloride (75 mL) and pre-adsorbed on silica gel (75 g). Flash chromatography on silica gel (725 g) eluting 5-, then 10-, and then 20% ethyl acetate-hexane gave the title compound (19 g, 83%, m.p. 58-61° C.) as a yellow-brown solid which was pure enough for further use.

Workup

  1. temperaturethe mixture was heated to reflux
  2. temperatureheated back
  3. temperatureto reflux for an additional 2 h
  4. temperatureAt this time the mixture was cooled to 23° C.
  5. filtrationThe mixture was filtered through Celite
  6. washwashed with ethyl acetate (2.2 L)
  7. customThe organic layer was separated from the filtrate
  8. washwashed with water and brine (2.2 L each)
  9. dry with materialdried (K2CO3)
  10. concentrationconcentrated in vacuo
  11. customto give the crude product (28 g) as a dark oil
  12. washFlash chromatography on silica gel (725 g) eluting 5-

Sources & evidence

ORD record
ord-29c814c1683b450ba81662525f2b5540
Source dataset
uspto-grants-2010_04
Patent number
US07696221B2

Reaction notes

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