3-Chlorophenol → HCID 54581864, compound

HRID 1442964Notes

Reaction equation

HRID 1442964 reaction equation
[CH3:1][O:2][C:3]([C@@H:5]1[CH2:9][C@@H:8]([OH:10])[CH2:7][N:6]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:4].[Cl:18][C:19]1[CH:20]=[C:21](O)[CH:22]=[CH:23][CH:24]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>COC(C)(C)C>[CH3:1][O:2][C:3]([C@@H:5]1[CH2:9][C@H:8]([O:10][C:23]2[CH:22]=[CH:21][CH:20]=[C:19]([Cl:18])[CH:24]=2)[CH2:7][N:6]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:4]

Participants

6

Reactant 4

HCID 79333-ChlorophenolHCID 11776TriphenylphosphineHCID 2734883(2S,4R)-4-Hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl esterHCID 5363146Diisopropyl azodicarboxylate

Product 1

HCID 54581864HCID 54581864, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent2×

Procedure

To a stirred solution of (2S,4R)-4-hydroxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (CAS Reg 74844-91-0) (6.1 kg, 24.87 mol), 3-chlorophenol (3.52 kg, 27.39 mol) & triphenylphosphine (7.18 kg, 27.37 mol) in tert-butyl methyl ether (30.5 L) at 0′C. was added diisopropylazodicarboxylate (5.53 kg, 27.35 mol) in tert-butyl methyl ether (15 L) dropwise. The mixture was stirred overnight at 20′C. The reaction was filtered and the liquors washed with 0.5M sodium hydroxide (aq) (2×12.5 L) & water (12.2 L). The tert-butyl methyl ether solvent was replaced with n-heptane (42.7 L) by atmospheric pressure distillation & cooled to crystallise crude product, which was collected by filtration (11.1 kg, 125% contaminated with ca 35% reduced diisopropyl dicarboxylate & triphenylphosphine oxide−corrected yield=86%).

Workup

  1. filtrationThe reaction was filtered
  2. washthe liquors washed with 0.5M sodium hydroxide (aq) (2×12.5 L) & water (12.2 L)
  3. distillationThe tert-butyl methyl ether solvent was replaced with n-heptane (42.7 L) by atmospheric pressure distillation
  4. temperaturecooled
  5. customto crystallise crude product, which
  6. filtrationwas collected by filtration (11.1 kg, 125% contaminated with ca 35% reduced diisopropyl dicarboxylate & triphenylphosphine oxide−corrected yield=86%)

Sources & evidence

ORD record
ord-5b04c20cfaae4c2b98aaf76344a1a742
Source dataset
uspto-grants-2010_02
Patent number
US07659305B2

Reaction notes

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