Diisopropylethylamine → (1R,2S,5R)-5-Methyl-2-(propan-2-yl)cyclohexyl N-(2-{[(tert-butoxy)carbonyl]amino}-2-methylcyclopentyl)carbamate

HRID 1750505Notes

Reaction equation

HRID 1750505 reaction equation
[NH2:1][CH:2]1[CH2:6][CH2:5][CH2:4][C:3]1([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH3:7].CCN(C(C)C)C(C)C.Cl[C:26]([O:28][C@@H:29]1[CH2:34][C@H:33]([CH3:35])[CH2:32][CH2:31][C@H:30]1[CH:36]([CH3:38])[CH3:37])=[O:27].C(=O)(O)[O-].[Na+]>C(Cl)Cl>[C:11]([O:10][C:9]([NH:8][C:3]1([CH3:7])[CH2:4][CH2:5][CH2:6][CH:2]1[NH:1][C:26](=[O:27])[O:28][C@@H:29]1[CH2:34][C@H:33]([CH3:35])[CH2:32][CH2:31][C@H:30]1[CH:36]([CH3:38])[CH3:37])=[O:15])([CH3:14])([CH3:13])[CH3:12]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 7014897Carbonochloridic acid, (1R,2S,5R)-5-methyl-2-(1-methylethyl)cyclohexyl esterHCID 84783510tert-Butyl N-(2-amino-1-methylcyclopentyl)carbamate2×

Product 1

HCID 118308072(1R,2S,5R)-5-Methyl-2-(propan-2-yl)cyclohexyl N-(2-{[(tert-butoxy)carbonyl]amino}-2-methylcyclopentyl)carbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of tert-butyl N-(2-amino-1-methylcyclopentyl)carbamate (Intermediate 24; 5.49 ml, 26.1 mmol) in DCM (87 ml) at 0° C. was added DIPEA (4.56 ml, 26.1 mmol) followed by (1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexyl chloroformate (CAS number 14602-86-9; 17.15 g, 78 mmol) drop wise. The reaction mixture was allowed to warm to room temperature and stirred overnight. The reaction was diluted with DCM (150 ml) and a saturated solution of sodium bicarbonate solution (200 ml). The aqueous layer was re-extracted with DCM (100 ml) and the combined organics were washed further with a saturated solution of sodium bicarbonate (100 ml), dried over magnesium sulfate and concentrated in vacuo. The residue was purified by column chromatography (silica, 0-50% ethyl acetate/petrol) to afford the title compound.

Workup

  1. extractionThe aqueous layer was re-extracted with DCM (100 ml)
  2. washthe combined organics were washed further with a saturated solution of sodium bicarbonate (100 ml)
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography (silica, 0-50% ethyl acetate/petrol)

Sources & evidence

ORD record
ord-418ff7e732c7441b99d8ff73ccedd0d1
Source dataset
uspto-grants-2015_10
Patent number
US09156829B2

Reaction notes

Loading…