Lithium Hydroxide → HCID 86701297, compound

HRID 1627032Notes

Reaction equation

HRID 1627032 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH2:17][O:18][CH2:19][C@H:20]([O:30][CH2:31][C:32]([CH3:34])=[CH2:33])[C@@H:21]([O:25][CH2:26][C:27]([CH3:29])=[CH2:28])[C@@H:22]([OH:24])[CH3:23])[C:13](OC)=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].[OH-].CC1C=CC=C([N+]([O-])=O)C=1C(OC(C1C([N+]([O-])=O)=CC=CC=1C)=O)=O>C1COCC1.O.CCOC(C)=O.C1(C)C=CC=CC=1.CN(C1C=CN=CC=1)C>[CH3:23][C@@H:22]1[O:24][C:13](=[O:14])[C@@H:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:17][O:18][CH2:19][C@H:20]([O:30][CH2:31][C:32]([CH3:34])=[CH2:33])[C@H:21]1[O:25][CH2:26][C:27]([CH3:29])=[CH2:28]

Participants

8

Reactant 3

HCID 3939Lithium HydroxideHCID 104726482-Methyl-6-nitrobenzoic anhydrideHCID 86701295HCID 86701295, compound

Product 1

HCID 86701297HCID 86701297, compoundYield 62.7%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolventHCID 21881883Oxolane--water (1/1)Solvent

Procedure

To a solution of (S)-methyl 2-(benzyloxycarbonylamino)-3-((2S,3S,4S)-4-hydroxy-2,3-bis(2-methylallyloxy)pentyloxy)propanoate (480 mg, 1.001 mmol) in THF/H2O (18 mL, 2:1 ratio) was added LiOH (71.9 mg, 3.00 mmol) and the solution was allowed to stir for 40 minutes (min) at ambient temperature. The crude reaction mixture was diluted with EtOAc and washed with 1 Normal (N) aqueous HCl. The phases were separated and the aqueous phase was extracted with EtOAc (3×20 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated to furnish the intermediate acid as a colorless oil which was dissolved in anhydrous toluene (50 mL) and added to a solution of MNBA (521 mg, 1.512 mmol) and DMAP (693 mg, 5.67 mmol) in toluene (180 mL) over the course of 3 h via syringe pump. After the addition was completed the reaction mixture was stirred for 1 h, concentrated, and purified by flash chromatography (SiO2) to afford the title compound as a white foam (281 mg, 62%): 1H NMR (400 MHz, CDCl3) δ 7.40-7.28 (m, 5H), 5.55 (d, J=7.7 Hz, 1H), 5.10 (s, 2H), 5.01-4.91 (m, 3H), 4.85 (d, J=1.2 Hz, 2H), 4.69 (dd, J=12.1, 6.7 Hz, 1H), 4.32 (d, J=11.7 Hz, 1H), 3.99-3.89 (m, 4H), 3.85 (d, J=11.3 Hz, 1H), 3.74 (dd, J=11.9, 4.5 Hz, 1H), 3.60-3.51 (m, 1H), 3.33-3.23 (m, 2H), 1.72 (d, J=6.2 Hz, 6H), 1.44 (d, J=6.3 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 170.85, 155.71, 142.26, 142.02, 136.10, 128.57, 128.25, 128.11, 112.33, 112.02, 84.95, 83.01, 77.63, 75.87, 74.89, 74.66, 72.86, 67.14, 54.26, 19.81, 19.66, 18.63; ESIMS m/z 470.3 ([M+Na]+).

Workup

  1. customThe crude reaction mixture
  2. washwashed with 1 Normal (N) aqueous HCl
  3. customThe phases were separated
  4. extractionthe aqueous phase was extracted with EtOAc (3×20 mL)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto furnish the intermediate acid as a colorless oil which
  9. additionAfter the addition
  10. stirringwas stirred for 1 h
  11. concentrationconcentrated
  12. custompurified by flash chromatography (SiO2)

Sources & evidence

ORD record
ord-bbf532c786df4d43ad97882ee0de4b2e
Source dataset
uspto-grants-2014_07
Patent number
US08785479B2

Reaction notes

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