Sodium Bicarbonate → alpha-(R)-(3-(S)-((4-(4-benzyl-5-methyl-1H-pyrazol-3(2H)-on-2-yl)-piperidin-1-yl)methyl)-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid 4-methoxybenzyl ester

HRID 1068182Notes

Reaction equation

HRID 1068182 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][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)=[O:16])[CH2:4]1)=O.[CH2:33]([C:40]1[C:41](=[O:52])[N:42]([CH:46]2[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]2)[NH:43][C:44]=1[CH3:45])[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+].C(=O)(O)[O-].[Na+]>ClCCCl.CO.CC(O)=O.C(OCC)(=O)C>[CH3:26][O:25][C:22]1[CH:21]=[CH:20][C:19]([CH2:18][O:17][C:15](=[O:16])[C@H:14]([N:5]2[CH2:6][C@H:7]([C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=3)[C@@H:3]([CH2:1][N:49]3[CH2:50][CH2:51][CH:46]([N:42]4[C:41](=[O:52])[C:40]([CH2:33][C:34]5[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=5)=[C:44]([CH3:45])[NH:43]4)[CH2:47][CH2:48]3)[CH2:4]2)[CH:27]2[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]2)=[CH:24][CH:23]=1

Participants

9

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 211931254-(4-benzyl-5-methyl-1H-pyrazole-3(2H)-on-2-yl)-piperidineHCID 53654320alpha-(R)-(3-(R)-formyl-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid 4-methoxybenzyl ester

Product 1

HCID 70124577alpha-(R)-(3-(S)-((4-(4-benzyl-5-methyl-1H-pyrazol-3(2H)-on-2-yl)-piperidin-1-yl)methyl)-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid 4-methoxybenzyl esterYield 9.7%

Reagents, catalysts & solvents 4

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 0.44 g of α-(R)-(3-(R)-formyl-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid 4-methoxybenzyl ester (prepared above as Aldehyde 5) and 0.55 g of 4-(4-benzyl-5-methyl-1H-pyrazole-3(2H)-on-2-yl)-piperidine in 3 mL 1,2-dichloroethane, 0.5 mL MeOH and 0.1 mL HOAc is added 0.3 g of powdered molecular sieves (4A). After 15 minutes, 0.1 g of sodium triacetoxyborohydride was added and stirring was continued overnight. The reaction mixture was poured into a rapidly stirred mixture of ethyl acetate and saturated sodium bicarbonate solution (˜15 mL each). After 15 minutes the mixture was filtered through Celite, the aqueous layer separated and extracted with 25 mL ethyl acetate. The combined organic layers were washed with saturated sodium bicarbonate solution, water, then brine, dried with sodium sulfate and concentrated under reduced pressure to give 0.068 g of α-(R)-(3-(S)-((4-(4-benzyl-5-methyl-1H-pyrazol-3(2H)-on-2-yl)-piperidin-1-yl)methyl)-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid 4-methoxybenzyl ester suitable for use in the next step. ESI-MS 691.3 (M+H); HPLC A: 3.20 min.

Workup

  1. waitwas continued overnight
  2. filtrationAfter 15 minutes the mixture was filtered through Celite
  3. customthe aqueous layer separated
  4. extractionextracted with 25 mL ethyl acetate
  5. washThe combined organic layers were washed with saturated sodium bicarbonate solution, water
  6. dry with materialbrine, dried with sodium sulfate
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-daf021e79cfd46f3ba42be7f3affcf1b
Source dataset
uspto-grants-2001_06
Patent number
US06248755B1

Reaction notes

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