Chloroacetic Acid → HCID 86590377, compound

HRID 349860Notes

Reaction equation

HRID 349860 reaction equation
[CH3:1][O:2][C:3](=[O:23])[C@H:4]([OH:22])[C@H:5]([NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[CH:8]=1.[Cl:24][CH2:25][C:26](O)=[O:27].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1C=CC=CC=1.CCCCCCC>[CH3:1][O:2][C:3](=[O:23])[C@@H:4]([O:22][C:26](=[O:27])[CH2:25][Cl:24])[C@H:5]([NH:14][C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[CH:8]=1

Participants

7

Reactant 4

HCID 300Chloroacetic AcidHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 69424236HCID 69424236, compound

Product 1

HCID 86590377HCID 86590377, compoundYield 43%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 8900HeptaneSolvent

Procedure

A solution of of the (2R,3R)-3-tert-butoxycarbonylamino-4-(3-fluoro-phenyl)-2-hydroxy-butyric acid methyl ester (8 g, 24.5 mmol, 1 eq), chloroacetic acid (5.79 g, 61.3 mmol, 2.5 eq), and PPh3 (16 g, 61.3 mmol, 2.5 eq) in benzene (340 mL) was cooled to 0 C followed by the addition of diethylazodicarboxylate (9.7 mL, 61.3 mmol, 2.5 eq) over a 20 min period. After the addition, the reaction mixture was stirred at ambient temperature for 2 h after which the reaction mixture was concentrated and the residue purified by column chromatography with 30% EtOAc/hexanes as eluant. Appropriate fractions were combined and concentrated to give a yellow solid which was shaken with heptane and filtered to remove the yellow DEAD residues. The product was thus obtained as a white solid (4.25 g, 43%) 1H NMR (CDCl3) 7.32 (m, 1H), 7.03–6.96 (m, 3H), 5.34 (d, J=3.5, 1H), 4.26 (s, 2H), 4.75–4.5 (series of m, 2H), 3.77 (s, 3H), 2.92 (bd, J=7, 2H), 1.43 (s, 9H).

Workup

  1. additionAfter the addition
  2. concentrationwas concentrated
  3. customthe residue purified by column chromatography with 30% EtOAc/hexanes as eluant
  4. concentrationconcentrated
  5. customto give a yellow solid which
  6. filtrationfiltered
  7. customto remove the yellow DEAD residues

Sources & evidence

ORD record
ord-1e714e08d0294a8fa69596af6c87ea31
Source dataset
uspto-grants-2007_02
Patent number
US07179918B2

Reaction notes

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