Sodium triacetoxyborohydride → alpha-(r)-(3-(s)-((4-(4-Benzyltriazol-2-yl)piperidin-1-yl)methyl)-4-(s)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid

HRID 1068173Notes

Reaction equation

HRID 1068173 reaction equation
[CH:1]([C@@H:3]1[C@@H:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:6][N:5]([C@H:14]([CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)[C:15]([O:17]CC2C=CC(OC)=CC=2)=[O:16])[CH2:4]1)=O.[CH2:33]([C:40]1[CH:44]=[N:43][N:42]([CH:45]2[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]2)[N:41]=1)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH2:33]([C:40]1[CH:44]=[N:43][N:42]([CH:45]2[CH2:50][CH2:49][N:48]([CH2:1][C@@H:3]3[C@@H:7]([C:8]4[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=4)[CH2:6][N:5]([C@H:14]([CH:27]4[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]4)[C:15]([OH:17])=[O:16])[CH2:4]3)[CH2:47][CH2:46]2)[N:41]=1)[C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 211930964-(4-Benzyltriazol-2-yl)piperidineHCID 53654320alpha-(R)-(3-(R)-formyl-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid 4-methoxybenzyl ester2×

Product 1

HCID 20664140alpha-(r)-(3-(s)-((4-(4-Benzyltriazol-2-yl)piperidin-1-yl)methyl)-4-(s)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acidYield 42%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A Solution of α-(R)-(3-(R)-Formyl-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid, para-methoxybenzyl ester (52 mg, 0.12 mmol, (prepared above as Aldehyde 5)), 4-(4-benzyltriazol-2-yl)piperidine (41 mg, 0.17 mmol from Step C) and sodium triacetoxyborohydride, (51 mg 0.24 mmol) in 1 mL of 1,2-dichloroethane was stirred for 12 h. The solvent was removed and the product was purified by preprative HPLC (column: YMC Combiprep ODS-A 20×50 mm, gradient: 5% acetonitrile/water w/0.1% TFA for 1 min then ramp to 100% acetonitrile w/0.1% TFA over 6 min, flow: 20 mL/min). The so isolated material was stirred in 3 mL formic acid for 16 h. After removal of solvent the residue was purified by ion exchange chromatography (3 grams SCX resin, 100% MeOH→2.0M NH3/MeOH) to give 17 mg (42%) of the title compound. 1H NMR (500 MHz, CD3OD). δ1.0-3.6 (m, 29H), 4.05 (s, 2H), 7.15-7.35 (m, 10H), ESI-MS. M/z; (M+H)=542.4 (obs), 542.34 (calc.).

Workup

  1. customThe solvent was removed
  2. customthe product was purified by preprative HPLC (column
  3. customfor 1 min
  4. customover 6 min
  5. stirringThe so isolated material was stirred in 3 mL formic acid for 16 h
  6. customAfter removal of solvent the residue
  7. customwas purified by ion exchange chromatography (3 grams SCX resin, 100% MeOH→2.0M NH3/MeOH)

Sources & evidence

ORD record
ord-7ed574e6f5e240afa678839a364f4440
Source dataset
uspto-grants-2001_06
Patent number
US06248755B1

Reaction notes

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