Lithium hydroxide, monohydrate → HCID 117974463, compound

HRID 708983Notes

Reaction equation

HRID 708983 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:14][O:15][CH2:16][C@H:17]([CH2:27][C:28]1[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=1)[C@@H:18]([O:22][CH2:23][CH:24]([CH3:26])[CH3:25])[C@@H:19]([OH:21])[CH3:20])[C:10]([O:12]C)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].O[Li].O>C1COCC1.O>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:14][O:15][CH2:16][C@H:17]([CH2:27][C:28]1[CH:29]=[CH:30][C:31]([CH3:34])=[CH:32][CH:33]=1)[C@@H:18]([O:22][CH2:23][CH:24]([CH3:25])[CH3:26])[C@@H:19]([OH:21])[CH3:20])[C:10]([OH:12])=[O:11])=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 117974488HCID 117974488, compound

Product 1

HCID 117974463HCID 117974463, compoundYield 85.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(((2S,3R,4S)-4-hydroxy-3-isobutoxy-2-(4-methylbenzyl)pentyl)oxy)propanoate (2.06 g, 4.28 mmol) in aqueous THF (16 THF:5 H2O; 21 mL total volume) was added LiOH—H2O (0.54 g, 12.83 mmol) and the reaction was stirred for 4 h at room temperature. The reaction was diluted with H2O (50 mL) and the majority of the THF was removed on the rotovap. The aqueous residue was acidified with 2 N HCl and extracted with CH2Cl2 (6×50 mL) until the aqueous phase was nearly clear. The combined organic extracts were washed with brine (2×50 mL), dried over Na2SO4, filtered, and concentrated to a colorless oil (1.96 g). The oil was purified by RP flash chromatography (C18; 0→85% CH3CN/H2O) to give (S)-2-((tert-butoxycarbonyl)amino)-3-(((2S,3R,4S)-4-hydroxy-3-isobutoxy-2-(4-methyl-benzyl)pentyl)oxy)-propanoic acid (1.71 g, 85%) as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 7.05 (m, 4H), 6.57 (s, 2H), 5.47 (d, J=8.1 Hz, 1H), 4.44 (m, 1H), 3.92 (m, 1H), 3.77 (m, 1H), 3.58 (m, 1H), 3.41 (d, J=7.2 Hz, 1H), 3.24 (m, 4H), 2.91 (dd, J=13.7, 4.0 Hz, 1H), 2.46 (dd, J=13.7, 10.8 Hz, 1H), 2.31 (s, 3H), 2.10 (dd, J=6.8, 3.3 Hz, 1H), 1.81 (dp, J=13.2, 6.6 Hz, 1H), 1.44 (s, 9H), 1.25 (d, J=6.2 Hz, 3H), 0.91 (dd, J=6.7, 2.7 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ 171.72, 153.71, 135.81, 133.44, 127.15, 127.02, 81.61, 78.33, 76.81, 69.13, 68.31, 67.08, 51.93, 40.98, 31.48, 27.16, 26.42, 19.12, 17.65, 17.58, 17.38; ESIMS m/z 491 ([M+Na]+).

Workup

  1. customthe majority of the THF was removed on the rotovap
  2. extractionextracted with CH2Cl2 (6×50 mL) until the aqueous phase
  3. washThe combined organic extracts were washed with brine (2×50 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated to a colorless oil (1.96 g)
  7. customThe oil was purified by RP flash chromatography (C18; 0→85% CH3CN/H2O)

Sources & evidence

ORD record
ord-b471ae8646464b4989a066ca1291cc04
Source dataset
uspto-grants-2015_11
Patent number
US09179674B2

Reaction notes

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