Dicyclohexylcarbodiimide → HCID 56981707, compound

HRID 426401Notes

Reaction equation

HRID 426401 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, 4H), 6.37 (s, 2H), 5.82 (t, J=6.1 Hz, 1H), 5.33 (d, J=5.2 Hz, 1H), 4.54 (s, 2H), 3.85 (s, 6H), 3.83 (s, 3H), 3.38 (d, J=12.6 Hz, 1H), 3.16 (td, J=12.8, 3.1 Hz, 1H), 2.60 (m, 2H), 2.45-2.05 (m, 3H), 1.70 (m, 6H), 1.50 (s, 9H), 1.45 (m, 2H), 1.25 (s, 3H), 1.23 (s, 3H), 0.90 (t, J=7.4 Hz, 3H); 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-a55e40c736e94f6aab040f8bebe35f49
Source dataset
uspto-grants-2012_01
Patent number
US08106191B2

Reaction notes

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