Dicyclohexylcarbodiimide → HCID 56981707, compound

HRID 368890Notes

Reaction equation

HRID 368890 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:13][CH2:14][C@H:15]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH2:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH:18]=2)[OH:16])[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].[O:32]=[C:33]([N:41]1[CH2:46][CH2:45][CH2:44][CH2:43][C@H:42]1[C:47](O)=[O:48])[C:34](=[O:40])[C:35]([CH3:39])([CH3:38])[CH2:36][CH3:37].C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)Cl.CN(C)C1C=CN=CC=1>[CH3:38][C:35]([CH3:39])([CH2:36][CH3:37])[C:34](=[O:40])[C:33]([N:41]1[CH2:46][CH2:45][CH2:44][CH2:43][C@H:42]1[C:47]([O:16][C@@H:15]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH2:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH:18]=1)[CH2:14][CH2:13][C:5]1[CH:4]=[C:3]([O:2][CH3:1])[C:8]([O:9][CH3:10])=[C:7]([O:11][CH3:12])[CH:6]=1)=[O:48])=[O:32]

Participants

6

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 5289328HCID 5289328, compoundHCID 53950128HCID 53950128, compound

Product 1

HCID 56981707HCID 56981707, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of alcohol 14 (650 mg, 1.5 mmol) in CH2Cl2 (5 mL) was treated with (2S)-1-(1,2-dioxo-3,3-dimethylpentyl)-2-piperidinecarboxylic acid (23, 382 mg, 1.5 mmol, followed by 1,3-dicyclohexylcarbodiimide (370 mg, 1.8 mmol), and 4-(dimethylamino)-pyridine (128 mg, 1.0 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, 20-30% EtOAc/hexanes) to give (1R)-3-(3,4,5-trimethoxyphenyl)-1-[3-(tert-butoxycarbonylmethoxy)phenyl]-1-propyl (2S)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-piperidinecarboxylate (776 mg, 78%) as a colorless oil: 1H NMR (CDCl3, 300 MHz) (single diastereomer, mixture of rotamers) 7.30-6.80 (m, 4 H), 6.37 (s, 2 H), 5.82 (t, J=6.1 Hz, 1 H), 5.33 (d, J=5.2 Hz, 1 H), 4.54 (s, 2 H), 3.85 (s, 6 H), 3.83 (s, 3 H), 3.38 (d, J=12.6 Hz, 1 H), 3.16 (td, J=12.8, 3.1 Hz, 1 H), 2.60 (m, 2 H), 2.45-2.05 (m, 3 H), 1.70 (m, 6 H), 1.50 (s, 9 H), 1.45 (m, 2 H), 1.25 (s, 3 H), 1.23 (s, 3 H), 0.90 (t, J=7.4 Hz, 3 H); 13C NMR (CDCl3, 75 MHz) (single diastereomer, mixture of rotamers) 208.2, 175.1, 170.1, 168.2, 167.6, 158.5, 153.6, 141.7, 137.0, 130.1, 120.9, 120.2, 114.6, 113.7, 105.7, 82.7, 66.2, 61.2, 56.5, 51.7, 47.1, 44.6, 38.2, 32.9, 32.4, 28.4, 26.8, 25.3, 23.9, 23.5, 21.6, 9.1.

Workup

  1. filtrationThe mixture was then filtered through glass wool
  2. customchromatographed (silica gel, 20-30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-6826c988df3e4f4483e537e60d1b5690
Source dataset
uspto-grants-2000_10
Patent number
US06133456

Reaction notes

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