Dichloromethane → (4-nitro-3-trifluoromethyl-phenyl)-(R)-pyrrolidin-3-yl-amine hydrochloride

HRID 511201Notes

Reaction equation

HRID 511201 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][C@@H:10]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[C:16]([C:23]([F:26])([F:25])[F:24])[CH:15]=2)[CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.[Cl:34]CCl>>[ClH:34].[N+:20]([C:17]1[CH:18]=[CH:19][C:14]([NH:13][C@@H:10]2[CH2:11][CH2:12][NH:8][CH2:9]2)=[CH:15][C:16]=1[C:23]([F:26])([F:24])[F:25])([O-:22])=[O:21]

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 58576068(R)-3-(4-nitro-3-trifluoromethyl-phenylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 67995634(4-nitro-3-trifluoromethyl-phenyl)-(R)-pyrrolidin-3-yl-amine hydrochloride

Procedure

To solid (R)-3-(4-Nitro-3-trifluoromethyl-phenylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester (1.12 g; 2.98 mmol, prepared in accordance with Example 164) is added a 3:2 mixture of dichloromethane and trifluoroacetic acid (5 mL) and the resulting solution is stirred at room temperature for 2 hours. All volatiles are then removed under high vacuum and the residue taken up in ethyl acetate. A 4 molar solution of hydrochloric acid in dioxane is then added and, after formation of an oily precipitate, all volatiles removed under high vacuum. The obtained residue is then taken up in methanol and treated with diethyl ether. This mixture is allowed to stand over night, concentrated under high vacuum and taken up in hot ethyl acetate. The solution is then allowed to stand at room temperature over night and the precipitate formed is collected and dried under high vacuum to afford the desired compound (1.07 g) which is used in the next step without further purification.

Workup

  1. customAll volatiles are then removed under high vacuum
  2. additionA 4 molar solution of hydrochloric acid in dioxane is then added
  3. customafter formation of an oily precipitate, all volatiles removed under high vacuum
  4. additiontreated with diethyl ether
  5. waitto stand over night
  6. concentrationconcentrated under high vacuum
  7. waitto stand at room temperature over night
  8. customthe precipitate formed
  9. customis collected
  10. customdried under high vacuum

Sources & evidence

ORD record
ord-97fd05671ad94a1384313fbe130c14e1
Source dataset
uspto-grants-2015_08
Patent number
US09096524B2

Reaction notes

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