(3R)-1-[(tert-butoxy)carbonyl]pyrrolidine-3-carboxylic acid → (3R)-1-tert-butoxycarbonyl-N-(9-chloro-3,4-dihydro-2H-1,5-benzodioxepin-7-ylmethyl)-N-isobutyl pyrrolidine-3-carboxamide

HRID 1024499

Reaction equation

HRID 1024499 reaction equation
[Cl:1][C:2]1[C:7]2[O:8][CH2:9][CH2:10][CH2:11][O:12][C:6]=2[CH:5]=[C:4]([CH2:13][NH:14][CH2:15][CH:16]([CH3:18])[CH3:17])[CH:3]=1.[C:19]([O:23][C:24]([N:26]1[CH2:30][CH2:29][C@@H:28]([C:31]([OH:33])=O)[CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20].Cl.C(N=C=NCCCN(C)C)C.CC1C=CN=C(N)C=1C>ClCCl.O>[C:19]([O:23][C:24]([N:26]1[CH2:30][CH2:29][C@@H:28]([C:31]([N:14]([CH2:13][C:4]2[CH:3]=[C:2]([Cl:1])[C:7]3[O:8][CH2:9][CH2:10][CH2:11][O:12][C:6]=3[CH:5]=2)[CH2:15][CH:16]([CH3:17])[CH3:18])=[O:33])[CH2:27]1)=[O:25])([CH3:20])([CH3:21])[CH3:22]

Participants

7

Reactant 4

HCID 1512491(3R)-1-[(tert-butoxy)carbonyl]pyrrolidine-3-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 110078842-Amino-3,4-dimethylpyridineHCID 43087680N-(9-chloro-3,4-dihydro-2H-1,5-benzodioxepin-7-ylmethyl)-2-methylpropan-1-amine

Product 1

HCID 66726406(3R)-1-tert-butoxycarbonyl-N-(9-chloro-3,4-dihydro-2H-1,5-benzodioxepin-7-ylmethyl)-N-isobutyl pyrrolidine-3-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of N-(9-chloro-3,4-dihydro-2H-1,5-benzodioxepin-7-ylmethyl)-2-methylpropan-1-amine (1,594 mg), (R)-Pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 1,270 mg, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (1,480 mg), dimethyl aminopyridine (1,030 mg) in 110 ml dichloromethane was stirred at room temperature overnight. After addition of water (75 mL), the mixture was extracted with ethyl acetate (100 mL 3). The organic layer was washed with saturated sodium bicarbonate, water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The product was purified by column chromatography on silica (33-50% ethyl acetate in hexane) and received as an oil: MS (m+1)=467.3.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (100 mL 3)
  2. washThe organic layer was washed with saturated sodium bicarbonate, water and brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe product was purified by column chromatography on silica (33-50% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-7de50193a91a4ff085b3939d957ad0fd
Source dataset
uspto-grants-2014_05
Patent number
US08722896B2

Linked notes

Loading…