Acetic Acid → (2S,3R)-3-(acetyloxy)-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid

HRID 1892149Notes

Reaction equation

HRID 1892149 reaction equation
N(C(OC(C)C)=O)=NC([O:5][CH:6](C)[CH3:7])=O.[OH:15][C@H:16]([CH2:34][CH2:35][C:36]1[CH:41]=[CH:40][C:39]([C:42]2[CH:43]=[N:44][C:45]([O:48][CH3:49])=[CH:46][CH:47]=2)=[CH:38][CH:37]=1)[C@H:17]([CH2:21][CH2:22][N:23]1[C:28](=[O:29])[C:27]2[CH:30]=[CH:31][CH:32]=[CH:33][C:26]=2[N:25]=[N:24]1)[C:18]([OH:20])=[O:19].C(P(CCCC)CCCC)CCC.C(O)(=O)C>O1CCCC1>[C:6]([O:15][C@H:16]([CH2:34][CH2:35][C:36]1[CH:37]=[CH:38][C:39]([C:42]2[CH:43]=[N:44][C:45]([O:48][CH3:49])=[CH:46][CH:47]=2)=[CH:40][CH:41]=1)[C@H:17]([CH2:21][CH2:22][N:23]1[C:28](=[O:29])[C:27]2[CH:30]=[CH:31][CH:32]=[CH:33][C:26]=2[N:25]=[N:24]1)[C:18]([OH:20])=[O:19])(=[O:5])[CH3:7]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 13831TributylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 66671252(2S,3R)-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid

Product 1

HCID 67182848(2S,3R)-3-(acetyloxy)-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acidYield 73.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Diisopropyl azodicarboxylate (63 mg) was added to a solution of compound (100 mg) obtained from Example 1A above, tri-n-butylphosphine (93 mg) and acetic acid (1 ml) in dry tetrahydrofuran (3 ml) at 0° C. Reaction mixture was stirred for 1 hour and concentrated. Residue was taken in ethyl acetate and washed with water and brine. Organic layer was concentrated to get oily residue which was purified on preparative thin layer chromatography (2 mm thickness) using 10% methanol in dichloromethane to get the title compound (80 mg) (formed probably by esterfication of acetic acid (used in large excess) and not due to Mitsunobu reaction). Mass (m/z): 517.06 (M++1); 1HNMR: δ 8.37 (m, 2H), 8.15 (d, 1H, J=8 Hz), 7.97-7.93 (m, 1H), 7.82-7.80 (m, 1H), 7.41 (d, 2H, J=8 Hz), 7.20 (d, 2H, J=8 Hz), 6.83 (d, 1H, J=8 Hz), 5.28-5.27 (m, 1H), 4.56-4.58 (m, 2H), 4.01 (s, 3H), 2.85-2.80 (m, 1H), 2.55-2.75 (m, 2H), 2.31-2.29 (m, 2H), 2.25-2.10 (m, 2H), 2.063 (s, 3H).

Workup

  1. customReaction mixture
  2. concentrationconcentrated
  3. washwashed with water and brine
  4. concentrationOrganic layer was concentrated
  5. customto get oily residue which
  6. customwas purified on preparative thin layer chromatography (2 mm thickness)

Sources & evidence

ORD record
ord-0b043cdab42a4525b118db922e74bdf8
Source dataset
uspto-grants-2013_08
Patent number
US08507670B2

Reaction notes

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