4-(3-Phenylpropyl)piperidine → 2-(R)-(3-(S)-((4-(3-Phenylpropyl)piperidin-1-yl)methyl)-4-(S)-phenylpyrrolidin-1-yl)-2-(cyclohexyl)acetic acid, benzyl ester

HRID 1386720Notes

Reaction equation

HRID 1386720 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:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)[C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])[CH2:4]1)=O.[C:31]1([CH2:37][CH2:38][CH2:39][CH:40]2[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]2)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[C:31]1([CH2:37][CH2:38][CH2:39][CH:40]2[CH2:41][CH2:42][N:43]([CH2:1][C@@H:3]3[C@@H:7]([C:8]4[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=4)[CH2:6][N:5]([C@H:14]([CH:25]4[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]4)[C:15]([O:17][CH2:18][C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)=[O:16])[CH2:4]3)[CH2:44][CH2:45]2)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

5

Reactant 3

HCID 876784-(3-Phenylpropyl)piperidineHCID 5049666Sodium triacetoxyborohydrideHCID 599246172-(R)-(3-(R)-formyl-4-(S)-phenylpyrrolidin-1-yl)-2-(cyclohexyl)acetic acid, benzyl ester

Product 1

HCID 1317228082-(R)-(3-(S)-((4-(3-Phenylpropyl)piperidin-1-yl)methyl)-4-(S)-phenylpyrrolidin-1-yl)-2-(cyclohexyl)acetic acid, benzyl esterYield 74.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 34 mg (0.084 mmol) of 2-(R)-(3-(R)-formyl-4-(S)-phenylpyrrolidin-1-yl)-2-(cyclohexyl)acetic acid, benzyl ester (from EXAMPLE 1, Step I) and 19 mg (0.093 mmol) of 4-(3-phenylpropyl) piperidine in 2 mL of CH2Cl2 at rt was added 27 mg (0.13 mmol) of sodium triacetoxyborohydride. After stirring for 1 h, the reaction was diluted with 25 mL of CH2Cl2 and washed with 25 mL of sat'd NaHCO3. After separating the phases, the aqueous layer was extracted with 25 mL of CH2Cl2. The combined organic phases were washed with 50 mL of sat'd NaCl, dried over MgSO4 and concentrated. The residue was purified by flash chromatography eluting with 50:1 v/v CH2Cl2/MeOH to give 37 mg (74%) of the title compound: 1H NMR (500 MHz) δ 0.99-2.91 (32H), 3.20-3.27 (3H1), 5.19 (ABq, J=19.7, 2H), 7.17-7.43 (15H); NH3-CI-MS 593 (M+H).

Workup

  1. washwashed with 25 mL of sat'd NaHCO3
  2. customAfter separating the phases
  3. extractionthe aqueous layer was extracted with 25 mL of CH2Cl2
  4. washThe combined organic phases were washed with 50 mL of sat'd NaCl
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography
  8. washeluting with 50:1 v/v CH2Cl2/MeOH

Sources & evidence

ORD record
ord-182e3c24126c4699b6bc1fbd77bcb47f
Source dataset
uspto-grants-2001_07
Patent number
US06265434B1

Reaction notes

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