Lithium Hydroxide → HCID 59664680, compound

HRID 2422380Notes

Reaction equation

HRID 2422380 reaction equation
[CH3:1][CH:2]([CH2:7][C:8]1[N:9]=[CH:10][N:11]([C:13]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:12]=1)[C:3]([O:5]C)=[O:4].[Li+].[OH-]>C1COCC1>[CH3:1][CH:2]([CH2:7][C:8]1[N:9]=[CH:10][N:11]([C:13]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:12]=1)[C:3]([OH:5])=[O:4]

Participants

4

Reactant 2

HCID 3939Lithium Hydroxide2×HCID 59664689HCID 59664689, compound

Product 1

HCID 59664680HCID 59664680, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The faster eluting enantiomer of methyl 2-methyl-3-(1-trityl-1H-imidazol-4-yl)propanoate (0.186 g, 0.453 mmol) was saponified by stirring in THF (2 mL) and 1 N LiOH (0.45 mL) for 2 hours. HPLC analysis shows 50% conversion to product. Nearly complete conversion (97.5%) required two additional additions of 1 N LiOH (0.1 mL each) and stirring for a total of 36 hrs. After concentrating under reduced pressure and addition of water (20 mL), the aqueous phase was extracted with DCM (3×20 mL) and the combined DCM extracts were washed with water, saturated sodium chloride (each 1×20 mL) and dried over MgSO4. The DCM was removed and the resulting solid was dried in vacuo to yield 0.1728 g of 97% pure (+)-2-methyl-3-(1-trityl-1H-imidazol-4-yl)propanoic acid; retention time, 9.36 min.; column: YMC ODS-A (3 μm, 50×4.6 mm); gradient: 10% to 100% B in A over 15 min. at 1.25 mL/min. Solvent A: 0.1% TFA in water, solvent B: 0.1% TFA in AcCN. LC/MS: ESI (M+H)+=397.30, (M−H)-=395.30. Optical rotation, [α]D=+12.8° (c=1.03 in CHCl3). 1H-NMR (CD3OD, 500 MHz): δ 1.13 (d, 3H), 2.57-2.65 (m, 1H), 2.67-2.80 (m, 1H), 2.82-2.92 (m, 1H), 6.75 (s, 1H), 7.10-7.17 (m, 6H), 7.34-7.41 (m, 9H), 7.58 (s, 1H).

Workup

  1. concentrationAfter concentrating under reduced pressure and addition of water (20 mL)
  2. extractionthe aqueous phase was extracted with DCM (3×20 mL)
  3. washthe combined DCM extracts were washed with water, saturated sodium chloride (each 1×20 mL) and
  4. dry with materialdried over MgSO4
  5. customThe DCM was removed
  6. customthe resulting solid was dried in vacuo

Sources & evidence

ORD record
ord-ac1d03bd6e75416eb0c3215c1793385b
Source dataset
uspto-grants-2011_06
Patent number
US07960349B2

Reaction notes

Loading…