Dicyclohexylcarbodiimide → HCID 57212849, compound

HRID 368889Notes

Reaction equation

HRID 368889 reaction equation
[C:1]1([CH2:7][CH2:8][C@H:9]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH:12]=2)[OH:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[O:26]=[C:27]([N:35]1[CH2:40][CH2:39][CH2:38][CH2:37][C@H:36]1[C:41](O)=[O:42])[C:28](=[O:34])[C:29]([CH3:33])([CH3:32])[CH2:30][CH3:31].C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)Cl.CN(C)C1C=CN=CC=1>[CH3:32][C:29]([CH3:33])([CH2:30][CH3:31])[C:28](=[O:34])[C:27]([N:35]1[CH2:40][CH2:39][CH2:38][CH2:37][C@H:36]1[C:41]([O:10][C@@H:9]([C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH:12]=1)[CH2:8][CH2:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)=[O:42])=[O:26]

Participants

6

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 5289328HCID 5289328, compoundHCID 53943160HCID 53943160, compound

Product 1

HCID 57212849HCID 57212849, compoundYield 82%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of alcohol 3 (342 mg, 1.0 mmol) in CH2Cl2 (3 mL) was treated with (2S)-1-(1,2-dioxo-3,3-dimethylpentyl)-2-piperidinecarboxylic acid (23, 255 mg, 1.0 mmol, prepared from L-pipecolic acid in 4 steps following literature procedures by Holt et al. J. Amer. Chem. Soc., 1993, 115, 9925-9938), followed by 1,3-dicyclohexylcarbodiimide (DCC, 247 mg, 1.2 mmol), and 4-(dimethylamino)-pyridine (DMAP, 85 mg, 0.70 mmol) under a nitrogen atmosphere. The resulting bright yellow suspension was allowed to stir overnight. The mixture was then filtered through glass wool and chromatographed (silica gel, 20% EtOAc/hexanes) to give (1R)-3-Phenyl-1-(3-(tert-butoxycarbonylmethoxy)phenyl]-1-propyl (2S)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-piperidinecarboxylate (470 mg, 82%) as a colorless oil: 1H NMR (CDCl3, 300 MHz) (single diastereomer, mixture of rotamers) 7.50-6.90 (m, 9 H), 5.93 (t, J=6.0 Hz, 1 H), 5.46 (d, J=3.4 Hz, 0.83 H, pipercolate α-H of rotamer A), 4.67 (s, 2 H), 3.50 (d, J=12.9 Hz, 1 H), 3.32 (td, J=12.5, 3.0 Hz, 1 H), 2.75 (m, 2 H), 2.53 (d, J=13.6 Hz, 1 H), 2.41 (m, 1 H), 2.22 (m, 1 H), 2.97-2.71 (m, 6 H), 1.62 (s, 9 H), 1.38 (s, 3 H), 1.35 (s, 3 H), 1.03 (t, J=7.4 Hz); 13C NMR (CDCl3, 75 MHz) (single diastereomer, mixture of rotamers) 208.3, 175.0, 170.0, 168.0, 167.5, 158.5, 141.7, 141.2, 130.2, 128.9, 128.7, 126.5, 120.2, 114.7, 113.6, 82.8, 66.1, 51.6, 47.1, 44.5, 38.2, 32.9, 32.0, 28.4, 26.8, 25.3, 24.0, 23.4, 21.6, 9.2. HRMS(FAB): (M+Na)+ calcd: 602.3094, found: 602.3090.

Workup

  1. filtrationThe mixture was then filtered through glass wool
  2. customchromatographed (silica gel, 20% EtOAc/hexanes)

Sources & evidence

ORD record
ord-a9d8f29a37724ebba735d05b9fba5fc7
Source dataset
uspto-grants-2000_10
Patent number
US06133456

Reaction notes

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