Triethylamine → tert-butyl 2-[2-(3 {[tert-butyl(dimethyl)silyl]oxy}phenyl)-4-(5-chloro-2-fluorophenyl)-2,5-dihydro-1H-pyrrol-1-yl]-1,1-dimethyl-2-oxoethylcarbamate

HRID 2054750Notes

Reaction equation

HRID 2054750 reaction equation
[Si:1]([O:8][C:9]1[CH:10]=[C:11]([CH:15]2[CH:19]=[C:18]([C:20]3[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][C:21]=3[F:27])[CH2:17][N:16]2[C:28](OC(C)(C)C)=[O:29])[CH:12]=[CH:13][CH:14]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(N(CC)CC)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[C:75]([O:79][C:80]([NH:82][C:83](C)([CH3:87])[C:84](O)=O)=[O:81])([CH3:78])([CH3:77])[CH3:76]>>[Si:1]([O:8][C:9]1[CH:10]=[C:11]([CH:15]2[CH:19]=[C:18]([C:20]3[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][C:21]=3[F:27])[CH2:17][N:16]2[C:28](=[O:29])[C:83]([NH:82][C:80](=[O:81])[O:79][C:75]([CH3:76])([CH3:78])[CH3:77])([CH3:87])[CH3:84])[CH:12]=[CH:13][CH:14]=1)([C:4]([CH3:6])([CH3:5])[CH3:7])([CH3:2])[CH3:3]

Participants

5

Reactant 4

HCID 8471TriethylamineHCID 2724699PyBOPHCID 2733845N-((1,1-dimethylethoxy)carbonyl)-2-methyl-alanineHCID 59682334tert-butyl 2-(3-{[tert-butyl(dimethyl)silyl]oxy)phenyl)-4-(5-chloro-2-fluorophenyl)-2,5-dihydro-1H-pyrrole-1-carboxylate

Product 1

HCID 59656598tert-butyl 2-[2-(3 {[tert-butyl(dimethyl)silyl]oxy}phenyl)-4-(5-chloro-2-fluorophenyl)-2,5-dihydro-1H-pyrrol-1-yl]-1,1-dimethyl-2-oxoethylcarbamate

Procedure

A solution of tert-butyl 2-(3-{[tert-butyl(dimethyl)silyl]oxy }phenyl)-4-(5-chloro-2-fluorophenyl)-2,5dihydro-1H-pyrrole-1-carboxylate (3-2, 276 mg, 0.683 mmol, 1 equiv), triethylamine (277 mg, 2.73 mmol, 4 equiv), PYBOP (711 mg, 1.37 mmol, 2 equiv) and 2-[(tert-butoxycarbonyl)amino]-2-methylpropanoic acid (278 mg, 1.37 mmol, 2 equiv) in in DMP (10 mL) was warmed at 60° C. for 18 h. The solution was concentrated and the residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The organic layer was washed with brine, dried over magnesium sulfate and concentrated. The residue was purified by flash column chromatography. Elution with 10% ethyl acetate/hexanes to 20% ethyl acetate/hexanes gave tert-butyl 2-[2-(3{[tert-butyl(dimethyl)silyl]oxy}phenyl)-4-(5-chloro-2-fluorophenyl)-2,5-dihydro-1H-pyrrol-1yl]-1,1-dimethyl-2-oxoethylcarbamate (3-3) as a pale yellow gum. LRMS n/z (M+H) 588.9 found, 589.0 required.

Workup

  1. concentrationThe solution was concentrated
  2. customthe residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution
  3. washThe organic layer was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by flash column chromatography
  7. washElution with 10% ethyl acetate/hexanes to 20% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-83344d523d4f40cdbbffbcdb37b37e59
Source dataset
uspto-grants-2008_02
Patent number
US07329762B2

Reaction notes

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