Lithium Hydroxide → HCID 67372392, compound

HRID 1677596Notes

Reaction equation

HRID 1677596 reaction equation
[CH2:1]([C:8]([NH:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])([CH2:30][OH:31])[CH2:9][O:10][CH2:11][C:12]1[CH:13]=[C:14]([C:26]([O:28]C)=[O:27])[CH:15]=[C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[C:24]#[N:25])[CH:17]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].[OH-]>C1COCC1.O>[CH2:1]([C:8]([NH:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])([CH2:30][OH:31])[CH2:9][O:10][CH2:11][C:12]1[CH:13]=[C:14]([C:26]([OH:28])=[O:27])[CH:15]=[C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[C:24]#[N:25])[CH:17]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 3939Lithium Hydroxide2×HCID 67372702HCID 67372702, compound

Product 1

HCID 67372392HCID 67372392, compoundYield 60.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of crude methyl 5-({2-benzyl-2-[(tert-butoxycarbonyl)-amino]-3-hydroxypropoxy}methyl)-2′-cyano-1,1′-biphenyl-3-carboxylate from step A (442 mg, 0.83 mmol) in 4 mL THF was added 1 N LiOH (1.25 mL, 1.25 mmol) and the reaction mixture was stirred at room temperature for 1.5 h. 1 N LiOH (1.25 mL, 1.25 mmol) was added and the reaction mixture was stirred at room temperature for 16 h. The reaction mixture was diluted with water, extracted with CH2Cl2 (3×), dried over sodium sulfate, concentrated in vacuo and purified by flash chromatography (90 g silica, 0->85% (0.5% HOAc in EtOAc)/hexanes) to provide 259 mg of 5-({2-benzyl-2-[(tert-butoxycarbonyl)amino]-3-hydroxypropoxy}methyl)-2′-cyano-1,1′-biphenyl-3-carboxylic acid as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 8.21 (s, 1H), 8.13 (s, 1H), 7.84 (s, 1H), 7.81 (d, J=7.7 Hz, 1H), 7.70 (t, J=7.3 Hz, 1H), 7.57 (d, J=7.7 Hz, 1H), 7.51 (t, J=7.3 Hz, 1H), 7.30-7.16 (m, 5H), 4.98 (s, 1H), 4.69 (A of AB, d, J=12.0 Hz, 1H), 4.65 (B of AB, d, J=12.0 Hz, 1H), 3.77 (A of AB, d, J=12.0 Hz, 1H), 3.69 (B of AB, d, J=12.0 Hz, 1H), 3.59 (A of AB, d, J=9.3 Hz, 1H), 3.69 (B of AB, d, J=9.3 Hz, 1H), 3.17 (A of AB, d, J=13.8 Hz, 1H), 2.93 (B of AB, d, J=13.8 Hz, 1H), 1.44 (s, 9H).

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 16 h
  2. extractionextracted with CH2Cl2 (3×)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. custompurified by flash chromatography (90 g silica, 0->85% (0.5% HOAc in EtOAc)/hexanes)

Sources & evidence

ORD record
ord-3842c730b8a34202bc7701633ffe29f8
Source dataset
uspto-grants-2011_08
Patent number
US08008315B2

Reaction notes

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