Triethylamine → 1,1-dimethylethyl 4-[[2-(1,1-dimethylethyl)-2H-tetrazol-5-yl]methyl]benzene propenoate

HRID 487816Notes

Reaction equation

HRID 487816 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[N:10]=[N:11][N:12]([C:14]([CH3:17])([CH3:16])[CH3:15])[N:13]=2)=[CH:4][CH:3]=1.[C:18]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])(=[O:21])[CH:19]=[CH2:20].C(N(CC)CC)C>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[C:18]([OH:22])(=[O:21])[CH:19]=[CH2:20].[CH3:24][C:23]([C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[N:10]=[N:11][N:12]([C:14]([CH3:17])([CH3:16])[CH3:15])[N:13]=2)=[CH:4][CH:3]=1)([CH3:26])[CH3:25]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 15458tert-Butyl acrylateHCID 148887015-[(4-Bromophenyl)methyl]-2-(1,1-dimethylethyl)-2H-tetrazole

Product 1

HCID 867465271,1-dimethylethyl 4-[[2-(1,1-dimethylethyl)-2H-tetrazol-5-yl]methyl]benzene propenoateYield 81%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of Pd(OAc)2 (90 mg, 0.42 mmol) and 1,1'-bis(diphenylphosphino)ferrocene (300 mg, 0.56 mmol) in DMF (40 mL) was heated at 90° C. for 15 minutes while argon was being passed through the mixture. After cooling the burgundy solution to ambient temperature. 5-[(4-bromophenyl) methyl]-2-(1,1-dimethylethyl)-2H-tetrazole (4.0 g. 14 mmol), t-butyl acrylate (3.1 g, 23 mmol) and triethylamine (2.8 mL, 20 mmol) were added to the mixture. The reaction was heated at 90° C. overnite and then concentrated. After filtering the dark mixture through a short column of silica gel using is a mixture of hexanes and ethyl acetate (4:1), the fractions containing product were pooled and concentrated. Final purification was achieved by chromatography on a Waters Prep 500 liquid chromatograph fitted with two silica gel cartridges eluting with a mixture of hexanes and ethyl acetate (9:1) to give pure 1,1-dimethylethyl 4-[[ 2-(1,1-dimethylethyl)-2H-tetrazol-5-yl]methyl]benzene propenoate (3.9 g. 11.3 mmol) in 81% yield. The analytical sample was recrystallized from ethyl acetate and hexanes, mp. 105°-106° C.

Workup

  1. temperatureAfter cooling the burgundy solution to ambient temperature
  2. temperatureThe reaction was heated at 90° C. overnite
  3. concentrationconcentrated
  4. filtrationAfter filtering the dark mixture through a short column of silica gel using
  5. additiona mixture of hexanes and ethyl acetate (4:1)
  6. additionthe fractions containing product
  7. concentrationconcentrated
  8. customFinal purification
  9. customfitted with two silica gel cartridges
  10. washeluting with a mixture of hexanes and ethyl acetate (9:1)

Sources & evidence

ORD record
ord-f8faaf12eb0b4f6f8a1ad2294792e703
Source dataset
uspto-grants-1994_03
Patent number
US05296608

Reaction notes

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