Lithium hydroxide, monohydrate → HCID 68792218, compound

HRID 1726439Notes

Reaction equation

HRID 1726439 reaction equation
C([O:3][C:4]([C@@:6]12[CH2:24][C@H:23]1[CH:22]=[CH:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][C@H:15]([NH:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C:14](=[O:33])[N:13]1[C@@H:9]([CH2:10][C@@H:11]([O:34][C:35]([N:37]3[CH2:45][C:44]4[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=4)[CH2:38]3)=[O:36])[CH2:12]1)[C:8](=[O:46])[NH:7]2)=[O:5])C.O[Li].O>C(Cl)Cl.CO>[C:29]([O:28][C:26]([NH:25][C@@H:15]1[C:14](=[O:33])[N:13]2[C@@H:9]([CH2:10][C@@H:11]([O:34][C:35]([N:37]3[CH2:38][C:39]4[C:44](=[CH:43][CH:42]=[CH:41][CH:40]=4)[CH2:45]3)=[O:36])[CH2:12]2)[C:8](=[O:46])[NH:7][C@@:6]2([C:4]([OH:5])=[O:3])[C@@H:23]([CH2:24]2)[CH:22]=[CH:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1)=[O:27])([CH3:32])([CH3:30])[CH3:31]

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 68787238HCID 68787238, compound

Product 1

HCID 68792218HCID 68792218, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

The macrocyclic ester product from Step D (60 mg, 0.092 mmol) was dissolved in 0.9 mL of a mixed solvent (THF/MeOH/H2O 2:1:1), followed by addition of LiOH—H2O (23 mg, 6 equiv). The mixture was stirred at rt for overnight. After 18 h, TLC (DCM/MeOH 9:1) showed a clean new spot with a lower Rf. The reaction was concentrated down to almost dryness and partitioned between 1N aq. HCl (15 mL) and DCM (20 mL). The aqueous layer was extracted with DCM (2×10 mL). The organic layers were combined, dried over Na2SO4 and concentrated down, giving the desired product as a white foamy powder (50 mg, 87%). 1H NMR (CDCl3, 500 MHz)  1.21-1.44 (m, 8H), 1.32 (s, 9H), 1.54-1.62 (m, 2H), 1.78-1.88 (m, 2H), 2.04-2.13 (m, 1H), 2.16-2.23 (m, 1H), 2.24-2.36 (m, 2H), 2.66-2.74 (m, 1H), 3.87-3.90 (m, 1H), 4.15 (d, J=11.0 Hz, 1H), 4.37-4.43 (m, 1H), 4.61-4.77 (m, 5H), 5.18 (t, J=10.3 Hz, 1H), 5.24-5.31 (m, 1H), 5.40-5.45 (m, 1H), 5.58-5.66 (m, 1H), 7.11-7.30 (m, 4H). MS m/z 611.0 (M++1).

Workup

  1. waitAfter 18 h
  2. concentrationThe reaction was concentrated down to almost dryness
  3. custompartitioned between 1N aq. HCl (15 mL) and DCM (20 mL)
  4. extractionThe aqueous layer was extracted with DCM (2×10 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated down

Sources & evidence

ORD record
ord-9f5fe53a8ff9423eb64badcb1d153f0a
Source dataset
uspto-grants-2009_02
Patent number
US07491794B2

Reaction notes

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