Water → HCID 117974593, compound

HRID 1776097Notes

Reaction equation

HRID 1776097 reaction equation
[CH2:1]([O:8][C@@H:9]([C@@H:42]([OH:44])[CH3:43])[C@@H:10]([CH2:33][C:34]1[CH:39]=[CH:38][C:37]([F:40])=[CH:36][C:35]=1[F:41])[CH2:11][CH2:12][CH2:13][C@H:14]([NH:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C:15]([O:17]CC1C=CC=CC=1)=[O:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1COCC1.O>Cl>[CH2:1]([O:8][C@@H:9]([C@@H:42]([OH:44])[CH3:43])[C@@H:10]([CH2:33][C:34]1[CH:39]=[CH:38][C:37]([F:40])=[CH:36][C:35]=1[F:41])[CH2:11][CH2:12][CH2:13][C@H:14]([NH:25][C:26]([O:28][C:29]([CH3:31])([CH3:32])[CH3:30])=[O:27])[C:15]([OH:17])=[O:16])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 962Water2×HCID 8028TetrahydrofuranHCID 117982166HCID 117982166, compound

Product 1

HCID 117974593HCID 117974593, compound

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

A 250 mL round bottom flask was charged with (2S,6R,7R,8S)-benzyl 7-(benzyloxy)-2-((tert-butoxycarbonyl)amino)-6-(2,4-difluorobenzyl)-8-hydroxynonanoate (2.10 g, 3.43 mmol), THF (24 mL) and H2O (6 mL). LiO.H2O (153 mg, 3.64 mmol) was added, and the resulting mixture was allowed to stir at room temperature. After stirring for 2.5 h, the reaction mixture was heated to 50° C. and was stirred for an additional 17 h at that temperature. Additional portions of water (3 mL) and LiO.H2O (152 mg, 3.62 mmol) were added and the reaction was stirred at room temperature for 4.5 h. The reaction mixture was diluted with 1.0 M aqueous HCl (50 mL) and extracted with EtOAc (3×50 mL). The combined organic extracts were washed with saturated aqueous sodium chloride solution (NaCl, brine; 50 mL), dried over anhydrous MgSO4, filtered, concentrated, and dried under high vacuum to obtain the title compound as a colorless oil contaminated with 10% BnOH (1.55 g, 87%): 1H NMR (400 MHz, CDCl3) δ 7.39-7.26 (m, 5H), 7.15-7.05 (m, 1H), 6.82-6.69 (m, 2H), 5.03 (d, J=8.3 Hz, 1H), 4.64 (d, J=11.5 Hz, 1H), 4.55 (d, J=11.6 Hz, 1H), 4.20 (q, J=7.4 Hz, 1H), 4.03 (p, J=6.2 Hz, 1H), 3.37-3.24 (m, 1H), 2.99 (dd, J=14.0, 4.6 Hz, 1H), 2.51 (dd, J=14.0, 9.9 Hz, 1H), 2.01-1.90 (m, 1H), 1.75-1.60 (m, 1H), 1.56-1.15 (m, 17H); 13C NMR (101 MHz, CDCl3) δ 176.51, 161.26 (dd, J=246.7, 12.7 Hz), 161.07 (dd, J=247.1, 12.0 Hz), 155.60, 138.35, 131.98 (dd, J=9.3, 6.9 Hz), 128.37, 127.77, 126.97, 124.00 (dd, J=15.8, 3.8 Hz), 110.83 (dd, J=20.8, 3.6 Hz), 104.38 102.95 (m), 83.36, 80.11, 73.75, 68.11, 53.17, 39.82, 32.49, 29.71, 28.85, 28.25, 22.55, 19.22; 19F NMR (376 MHz, CDCl3) δ −113.45 (d, J=7.0 Hz), −113.63 (d, J=6.7 Hz); ESIMS: m/z 522 ([M+H]+).

Workup

  1. stirringAfter stirring for 2.5 h
  2. temperaturethe reaction mixture was heated to 50° C.
  3. stirringwas stirred for an additional 17 h at that temperature
  4. stirringthe reaction was stirred at room temperature for 4.5 h
  5. extractionextracted with EtOAc (3×50 mL)
  6. washThe combined organic extracts were washed with saturated aqueous sodium chloride solution (NaCl, brine; 50 mL)
  7. dry with materialdried over anhydrous MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customdried under high vacuum

Sources & evidence

ORD record
ord-6ce8e822836d4592a9a4e4fc2c8b8694
Source dataset
uspto-grants-2016_02
Patent number
US09265253B2

Reaction notes

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