4-Methylmorpholine → Tert-butyl 4,4-difluoro-2-[4-(5-fluoropyridin-2-yl)benzyl]-2-{[(2-hydroxy-4,4-dimethylhexyl)amino]carbonyl}pyrrolidine-1-carboxylate

HRID 1881497Notes

Reaction equation

HRID 1881497 reaction equation
CN1CCOCC1.[C:8]([O:12][C:13]([N:15]1[CH2:22][C:21]([F:24])([F:23])[CH2:20][C@@:16]1([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][N:33]=2)=[CH:28][CH:27]=1)[C:17]([OH:19])=O)=[O:14])([CH3:11])([CH3:10])[CH3:9].[NH2:39][CH2:40][CH:41]([OH:48])[CH2:42][C:43]([CH3:47])([CH3:46])[CH2:44][CH3:45].Cl.CN(C)CCCN=C=NCC.OC1C2N=NNC=2C=CC=1>ClCCl>[F:23][C:21]1([F:24])[CH2:22][N:15]([C:13]([O:12][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:14])[C:16]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([C:32]3[CH:37]=[CH:36][C:35]([F:38])=[CH:34][N:33]=3)=[CH:28][CH:27]=2)([C:17]([NH:39][CH2:40][CH:41]([OH:48])[CH2:42][C:43]([CH3:47])([CH3:46])[CH2:44][CH3:45])=[O:19])[CH2:20]1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 55289824HCID 55289824, compoundHCID 667056251-(Tert-butoxycarbonyl)-4,4-difluoro-2-[4-(5-fluoropyridin-2-yl)benzyl]prolineHCID 178418300HCID 178418300, compound

Product 1

HCID 66705621Tert-butyl 4,4-difluoro-2-[4-(5-fluoropyridin-2-yl)benzyl]-2-{[(2-hydroxy-4,4-dimethylhexyl)amino]carbonyl}pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-methylmorpholine (0.2 mL, 1.8 mmol) was added to a solution of 1-(tert-butoxycarbonyl)-4,4-difluoro-2-[4-(5-fluoropyridin-2-yl)benzyl]proline (175 mg, 0.40 mmol), 1-amino-4,4-dimethylhexan-2-ol (58 mg, 0.40 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (92 mg, 0.48 mmol), and hydroxybenzotriazole (65 mg, 0.48 mmol) in dichloromethane (40 mL). After stirring at ambient temperature overnight, the reaction mixture was washed with saturated aqueous sodium bicarbonate, dried (magnesium sulfate), filtered, and concentrated in vacuo to afford tert-butyl 4,4-difluoro-2-[4-(5-fluoropyridin-2-yl)benzyl]-2-{[(2-hydroxy-4,4-dimethylhexyl)amino]carbonyl}-pyrrolidine-1-carboxylate which was used in the subsequent step without further purification.

Workup

  1. washthe reaction mixture was washed with saturated aqueous sodium bicarbonate
  2. dry with materialdried (magnesium sulfate)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2e68b8d570e14820b5b580848eb7358e
Source dataset
uspto-grants-2012_11
Patent number
US08318767B2

Reaction notes

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