Diethyl Ether → 2-(3-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2-oxoazepan-1-yl)acetic acid

HRID 393048Notes

Reaction equation

HRID 393048 reaction equation
[NH2:1][CH:2]1[CH2:8][CH2:7][CH2:6][CH2:5][N:4]([CH2:9][C:10]([OH:12])=[O:11])[C:3]1=[O:13].C(=O)([O-])O.[Na+].[CH:19]1[C:31]2[CH:30]([CH2:32][O:33][C:34](ON3C(=O)CCC3=O)=[O:35])[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:23]=2[CH:22]=[CH:21][CH:20]=1.CCOCC>O.O1CCCC1>[CH:19]1[C:31]2[CH:30]([CH2:32][O:33][C:34]([NH:1][CH:2]3[CH2:8][CH2:7][CH2:6][CH2:5][N:4]([CH2:9][C:10]([OH:12])=[O:11])[C:3]3=[O:13])=[O:35])[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:23]=2[CH:22]=[CH:21][CH:20]=1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 134122N-(9-Fluorenylmethoxycarbonyloxy)succinimideHCID 516892Sodium BicarbonateHCID 137494963-Aminohexahydro-2-oxo-1H-azepine-1-acetic acid

Product 1

HCID 47126032-(3-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2-oxoazepan-1-yl)acetic acidYield 98%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

3-Aminohexahydro-2-oxo-1H-azepine-1-acetic acid (which can be prepared by the procedure of Thorsett, E. D. et al. J. Med. Chem. 1986, 29, 251-260; 9.3 g, 50 mmol) was added to a solution of sodium hydrogen carbonate (5 g, 60 mmol) in water (100 mL). A solution of 1-[[(9H-fluoren-9-ylmethoxy)carbonyl]oxy-2,5-pyrrolidinedione (Fmoc-OSu; 18.6 g, 55 mmol) in tetrahydrofuran (110 mL) was added. The solution was stirred at room temperature overnight and then ether (200 mL) was added. The layers were separated and the organic layer was back-extracted with saturated sodium hydrogen carbonate-water (1:1; 60 mL). The combined aqueous layers were acidified with 1 M HCl (110 mL). The solid was filtered off, washed with water (4×20 mL), and dried in vacuo to give 3-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]hexahydro-2-oxo-1H-azepine-1-acetic acid (20.1 g, 98%) as a white solid, mp 118° C. (dec.)

Workup

  1. customThe layers were separated
  2. extractionthe organic layer was back-extracted with saturated sodium hydrogen carbonate-water (1:1; 60 mL)
  3. filtrationThe solid was filtered off
  4. washwashed with water (4×20 mL)
  5. customdried in vacuo

Sources & evidence

ORD record
ord-fa55e30b429846bab1cb50d4850df8ba
Source dataset
uspto-grants-2004_10
Patent number
US06803384B2

Reaction notes

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