Hydrochloric Acid → Cyclohexyl-{(S)-3-[4-hydroxy-4-(3-phenyl-propyl)-piperidin-1-ylmethyl]-4-phenyl-pyrrolidin-1-yl}-acetic acid benzyl ester

HRID 1386669Notes

Reaction equation

HRID 1386669 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.[OH:31][C:32]1([CH2:38][CH2:39][CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1.Cl.CCN(C(C)C)C(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[OH:31][C:32]1([CH2:38][CH2:39][CH2:40][C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=2)[CH2:37][CH2:36][N:35]([CH2:1][C@@H:3]2[C@@H:7]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[CH2:6][N:5]([C@H:14]([CH:25]3[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]3)[C:15]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[O:16])[CH2:4]2)[CH2:34][CH2:33]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 4169034-(3-Phenylpropyl)piperidin-4-olHCID 5049666Sodium triacetoxyborohydrideHCID 599246172-(R)-(3-(R)-formyl-4-(S)-phenylpyrrolidin-1-yl)-2-(cyclohexyl)acetic acid, benzyl ester

Product 1

HCID 501044Cyclohexyl-{(S)-3-[4-hydroxy-4-(3-phenyl-propyl)-piperidin-1-ylmethyl]-4-phenyl-pyrrolidin-1-yl}-acetic acid benzyl esterYield 86%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 87 mg (0.21 mmol) of 2-(R)-(3-(R)-formyl-4-(S)-phenylpyrrolidin-1-yl)-2-(cyclohexyl)acetic acid, benzyl ester (from EXAMPLE 1, Step I) and 69 mg (0.26 mmol) of 4hydroxy-4-(3-phenylpropyl)-piperidine.HCl in 5 mL of CH2Cl2 at rt was treated with 0.045 mL (0.25 mmol) of DIEA and 86 mg (0.40 mmol) of sodium triacetoxyborohydride and stirred at rt for 1 h. The reaction was diluted with 25 mL of CH2Cl2 and washed with 25 mL of 1.0 N NaHCO3. The layers were separated and 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 Na2SO4 and concentrated. Flash chromatography on silica gel using 50:1 v/v CH2Cl2/MeOH as the eluant afforded 110 mg (83%) of the title compound: RF: 0.46 (20:1 v/v CH2Cl2/MeOH); 1H NMR (300 MHz) δ 0.91-2.85 (m, 32H), 3.16-3.27 (m, 3H), 5.15 (ABq, J=12.2 Hz, 2H), 7.15-7.41 (m, 15H); NH3-CI-MS 609 (M+H).

Workup

  1. washwashed with 25 mL of 1.0 N NaHCO3
  2. customThe layers were separated
  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 Na2SO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-4c785804885242b89ed709ffe5d20169
Source dataset
uspto-grants-2001_07
Patent number
US06265434B1

Reaction notes

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