Sodium borohydride → (2-Butyl-4-chloro-1-((2'-(1-trityl-1H-tetraazol-5-YL)(1,1'-biphenyl)-4-YL)methyl)-1H-imidazol-5-YL)methanol

HRID 1746866Notes

Reaction equation

HRID 1746866 reaction equation
[CH2:1]([C:5]1[N:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:23]3[N:27]([C:28]([C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=4)([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)[C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[N:26]=[N:25][N:24]=3)=[CH:13][CH:12]=2)[C:8]([CH:47]=[O:48])=[C:7]([Cl:49])[N:6]=1)[CH2:2][CH2:3][CH3:4].[BH4-].[Na+]>CCO>[CH2:1]([C:5]1[N:9]([CH2:10][C:11]2[CH:12]=[CH:13][C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:23]3[N:27]([C:28]([C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=4)([C:35]4[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=4)[C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[N:26]=[N:25][N:24]=3)=[CH:15][CH:16]=2)[C:8]([CH2:47][OH:48])=[C:7]([Cl:49])[N:6]=1)[CH2:2][CH2:3][CH3:4]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 11657587N-Trityl Losartan Carboxaldehyde

Product 1

HCID 11643218(2-Butyl-4-chloro-1-((2'-(1-trityl-1H-tetraazol-5-YL)(1,1'-biphenyl)-4-YL)methyl)-1H-imidazol-5-YL)methanolYield 90%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To an EtOH (500 mL) solution of intermediate (11a) (41.0 g, 61.8 mmol) was added solid NaBH4 (2.8 g, 74.1 mmol). The mixture was stirred at room temperature for 1 hour. After cooling to 0° C., the reaction was quenched by dropwise addition of a 50/50 solution of acetic acid/water until no effervescence was observed. EtOAc (500 mL) was added and the organic was washed three times with saturated aqueous NaCl (100 mL). Solvent was removed and purification was achieved by silica gel chromatography (50:50 EtOAc:hexanes) using an isocratic gradient to provide intermediate (11b) as a white solid (37 g). MS m/z: [M+H+] calcd for C41H37ClN6O, 665.28. found 665.3. 1H-NMR (d4-MeOH): 0.79 (m, 3H), 1.20 (m, 2H), 1.46 (m, 2H), 2.45 (m, 2H), 4.30 (s, 2H), 5.19 (s, 2H), 6.83-6.90 (m, 8H), 7.05 (d, 2H), 7.23-7.33 (m, 10H), 7.53 (m, 2H), 7.81 (d, 1H).

Workup

  1. temperatureAfter cooling to 0° C.
  2. customthe reaction was quenched by dropwise addition of a 50/50 solution of acetic acid/water until no effervescence
  3. additionEtOAc (500 mL) was added
  4. washthe organic was washed three times with saturated aqueous NaCl (100 mL)
  5. customSolvent was removed
  6. custompurification

Sources & evidence

ORD record
ord-de140226977e401b86d691fc430a6d87
Source dataset
uspto-grants-2015_10
Patent number
US09150514B2

Reaction notes

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