HCID 71014552, compound → HCID 71014666, compound

HRID 1503649Notes

Reaction equation

HRID 1503649 reaction equation
C(OC([NH:11][C@H:12]([C:35]([O:37]C)=[O:36])[CH2:13][CH2:14][P:15]([CH:18]([C:20]1[CH:25]=[C:24]([F:26])[C:23]([O:27][CH2:28][C:29]([O:31]CC)=[O:30])=[C:22]([F:34])[CH:21]=1)[OH:19])(=[O:17])[OH:16])=O)C1C=CC=CC=1>Cl>[NH2:11][CH:12]([CH2:13][CH2:14][P:15]([CH:18]([C:20]1[CH:25]=[C:24]([F:26])[C:23]([O:27][CH2:28][C:29]([OH:31])=[O:30])=[C:22]([F:34])[CH:21]=1)[OH:19])([OH:17])=[O:16])[C:35]([OH:37])=[O:36]

Participants

3

Reactant 1

HCID 71014552HCID 71014552, compound

Product 1

HCID 71014666HCID 71014666, compoundYield 62.6%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

A solution of ((S)-3-(((benzyloxy)carbonyl)amino)-4-methoxy-4-oxobutyl)((4-(2-ethoxy-2-oxoethoxy)-3,5-difluorophenyl)(hydroxy)methyl)phosphinic acid (552 mg, 0.99 mmol) in 6 N HCl (6M) was refluxed during 3 h. Then, the mixture was cooled to room temperature and the solvent was evaporated under vacuum. The residue was diluted in EtOAc (50 mL) and extracted with 1 N HCl (2×80 mL). The combined aqueous layers were washed twice with EtOAc and the solvent was evaporated to afford 238 mg (0.62 mmol) of crude product which was purified by cation (and anion) exchange resin chromatography. Cation exchange resin chromatography: 238 mg of crude compound were deposited on a Dowex AG 50W-X4, H+, 50-100 mesh. The compound was eluted with water and 85 mg of desired product were collected. Anion exchange resin chromatography: 85 mg of compound were deposited on a Dowex AG 50W-X4, AcO−, 200-400 mesh. The compound was eluted with boiled water and formic acid. 27 mg (yield 7% on 2 steps) of pure product derivative 28 were collected (2 M HCOOH). 1H NMR (250 MHz; D2O) δ (ppm): 1.87 (m, 2H); 2.17 (m, 2H); 4.13 (m, 1H); 4.87 (s, 2H); 4.94 (d, JHP=9.4 Hz, 1H); 7.13 (d, J=9.1 Hz, 2H). 13C NMR (63 MHz; D2O) δ (ppm): 21.7 (d, JCP=91.0 Hz); 22.8; 53.1 (d, JCP=14.8 Hz); 69.8; 71.3 (d, JCP=109.5 Hz); 110.8 (dd, JCF=23.3 Hz and 4.0 Hz); 133.2 (t, JCF=14.0 Hz); 134.0 (t, JCF=8.1 Hz); 154.7 (dd, JCF=246.6 Hz and 5.4 Hz); 171.4; 172.9. 31P NMR (200 MHz; D2O) δ (ppm): 41.5 (s). 19F NMR (376 MHz: D2O) δ (ppm): −129.0 (s) MS (ESI) m/z: 384 [M+H+]. HPLC: tR=10.1 min

Workup

  1. customthe solvent was evaporated under vacuum
  2. additionThe residue was diluted in EtOAc (50 mL)
  3. extractionextracted with 1 N HCl (2×80 mL)
  4. washThe combined aqueous layers were washed twice with EtOAc
  5. customthe solvent was evaporated

Sources & evidence

ORD record
ord-edf30e04aefe4228a6e44a190c6737cd
Source dataset
uspto-grants-2015_12
Patent number
US09212196B2

Reaction notes

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