Acetic Acid → 1-tert-Butyl 2-methyl (2S)-4-(4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidin-1-yl)pyrrolidine-1,2-dicarboxylate

HRID 2233944Notes

Reaction equation

HRID 2233944 reaction equation
[CH3:1][O:2][C:3](=[O:17])[C@@H:4]1[CH2:8][C@@H:7](O)[CH2:6][N:5]1[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11].Cl.[Cl:19][C:20]1[C:24]([Cl:25])=[C:23]([CH3:26])[NH:22][C:21]=1[C:27]([NH:29][CH:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1)=[O:28].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>ClCCCl.CCOCC>[Cl:19][C:20]1[C:24]([Cl:25])=[C:23]([CH3:26])[NH:22][C:21]=1[C:27]([NH:29][CH:30]1[CH2:35][CH2:34][N:33]([CH:7]2[CH2:6][N:5]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C@H:4]([C:3]([O:2][CH3:1])=[O:17])[CH2:8]2)[CH2:32][CH2:31]1)=[O:28]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 2734883(2S,4R)-4-Hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl esterHCID 5049666Sodium triacetoxyborohydrideHCID 68579996HCID 68579996, compound2×

Product 1

HCID 866082951-tert-Butyl 2-methyl (2S)-4-(4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidin-1-yl)pyrrolidine-1,2-dicarboxylate

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 3283Diethyl EtherSolvent

Procedure

N-BOC-trans-4-Hydroxy-L-proline methylester (0.20 g, 0.81 mM) and 3,4-dichloro-5-methyl-N-piperidin-4-yl-1H-pyrrole-2-carboxamide (free base of Intermediate 1), 0.16 g, 0.81 mM) were stirred in 1,2-dichloroethane (3.5 ml). Sodium triacetoxyborohydride (0.24 g, 1.1 mM) was added followed by acetic acid (0.05 ml). The reaction was stirred under nitrogen at room temperature overnight then diluted with ether and washed with 1 N sodium hydroxide. The organic phase was washed with brine, dried over MgSO4 and concentrated to give an orange oil. The oil was chromatographed using EtOAc to give the desired product as a light yellow solid.

Workup

  1. washwashed with 1 N sodium hydroxide
  2. washThe organic phase was washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customto give an orange oil
  6. customThe oil was chromatographed

Sources & evidence

ORD record
ord-3f684d12d6864294a450c20e06ae6240
Source dataset
uspto-grants-2010_05
Patent number
US07709503B2

Reaction notes

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