Triphenylphosphine → 3-{[Methoxycarbonylmethyl-(toluene-4-sulfonyl)-amino]-methyl}-pyridine-2-carboxylic Acid Isopropyl Ester

HRID 897272Notes

Reaction equation

HRID 897272 reaction equation
O[CH2:2][C:3]1[C:4]([C:9]([O:11][CH:12]([CH3:14])[CH3:13])=[O:10])=[N:5][CH:6]=[CH:7][CH:8]=1.[CH3:15][C:16]1[CH:21]=[CH:20][C:19]([S:22]([NH:25][CH2:26][C:27]([O:29][CH3:30])=[O:28])(=[O:24])=[O:23])=[CH:18][CH:17]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[CH:12]([O:11][C:9]([C:4]1[C:3]([CH2:2][N:25]([CH2:26][C:27]([O:29][CH3:30])=[O:28])[S:22]([C:19]2[CH:18]=[CH:17][C:16]([CH3:15])=[CH:21][CH:20]=2)(=[O:24])=[O:23])=[CH:8][CH:7]=[CH:6][N:5]=1)=[O:10])([CH3:14])[CH3:13]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 562880Methyl 2-(4-methylphenylsulfonamido)acetateHCID 5462977Diethyl azodicarboxylate2×HCID 22346407Propan-2-yl 3-(hydroxymethyl)pyridine-2-carboxylate

Product 1

HCID 599831603-{[Methoxycarbonylmethyl-(toluene-4-sulfonyl)-amino]-methyl}-pyridine-2-carboxylic Acid Isopropyl Ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Isopropyl 3-(hydroxymethyl)pyridine-2-carboxylate, (200 g, 1.02 mol; prepared as in P. Ornstein et. al. J. Med. Chem. 1989, 32, 827), methyl N-[(4-methylphenyl)sulfonyl]glycinate (249 g, 1.02 mol), and triphenylphosphine (403 g, 1.5 mol) were dissolved in dry THF (3000 mls) and cooled to zero degrees under N2. The diethylazodicarboxylate (DEAD) (267.6 g, 1.5 mol) was dissolved in dry THF (250 mls) and placed in a 500 ml addition funnel. The DEAD was added dropwise over 1 hour. The ice bath was removed and the reaction was allowed to warm slowly to RT. After 2 hours, the reaction was checked by HPLC and some glycinate remained. More starting reagents were added and the reaction was left to stir at RT. After 30 min, the reaction was checked again and saw a very small amount of the glycinate remaining. Concentrated reaction down to a reddish-orange oil that was carried onto the next step.

Workup

  1. temperaturecooled to zero degrees under N2
  2. additionplaced in a 500 ml addition funnel
  3. customThe ice bath was removed
  4. additionwere added
  5. waitthe reaction was left
  6. waitAfter 30 min
  7. concentrationConcentrated
  8. customreaction down to a reddish-orange oil that

Sources & evidence

ORD record
ord-233afd09c83942ab9e04dae5919d6d92
Source dataset
uspto-grants-2005_07
Patent number
US06921759B2

Reaction notes

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