Tripropylamine → 1-(4-Methoxy-benzenesulfonyl)-3-(4-methoxy-benzyloxycarbonyl-amino)-2,3,4,7-tetrahydro-1H-azepine-2-carboxylic Acid Tert-Butyl Ester

HRID 1872259Notes

Reaction equation

HRID 1872259 reaction equation
[C:1]([O:5][C:6]([CH:8]1[CH:14](C(O)=O)[CH2:13][CH:12]=[CH:11][CH2:10][N:9]1[S:18]([C:21]1[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=1)(=[O:20])=[O:19])=[O:7])([CH3:4])([CH3:3])[CH3:2].C([N:32]([CH2:36]CC)CCC)CC.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:46])C=CC=CC=1.[CH3:56][O:57][C:58]1[CH:65]=[CH:64][C:61]([CH2:62][OH:63])=[CH:60][CH:59]=1>O1CCCC1>[C:1]([O:5][C:6]([CH:8]1[CH:14]([NH:32][C:36]([O:63][CH2:62][C:61]2[CH:64]=[CH:65][C:58]([O:57][CH3:56])=[CH:59][CH:60]=2)=[O:46])[CH2:13][CH:12]=[CH:11][CH2:10][N:9]1[S:18]([C:21]1[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=1)(=[O:20])=[O:19])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 7616TripropylamineHCID 77384-Methoxybenzyl alcoholHCID 199401P,P-Diphenylphosphinic azideHCID 155505231-(4-Methoxy-benzenesulfonyl)-2,3,4,7-tetrahydro-1H-azepine-2,3-dicarboxylic acid 2-tert-butyl ester

Product 1

HCID 155505251-(4-Methoxy-benzenesulfonyl)-3-(4-methoxy-benzyloxycarbonyl-amino)-2,3,4,7-tetrahydro-1H-azepine-2-carboxylic Acid Tert-Butyl Ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The reaction is performed under an Argon atmosphere and exclusion of light. 1-(4-Methoxy-benzenesulfonyl)-2,3,4,7-tetrahydro-1H-azepine-2,3-dicarboxylic acid 2-tert-butyl ester (550 mg, 1.34 mmol) is dissolved in 7 ml dry Tetrahydrofuran (THF). Tripropyl amine (TPA) (280 μl, 1.47 mmol) is added and the reaction is stirred for 30 minutes at RT. Diphenyl phosphoryl azide (318 μl, 1.47 mmol) is added and the reaction is gradually heated to 40° C. for 3 h. The reaction temperature is then increased to reflux conditions for 6 h. The reaction mixture is allowed to cool to room temperature and 4-Methoxybenzylalcohol (184 μl, 1.47 mmol) is added. The reaction is heated to reflux over night. The solvent is evaporated. Flash-chromatography Hexane/Ethylacetate (2:1) afforded the product: Cal. 383.5 found (MH)+ 383.0.

Workup

  1. temperaturethe reaction is gradually heated to 40° C. for 3 h
  2. temperatureThe reaction temperature is then increased
  3. temperatureto reflux conditions for 6 h
  4. temperatureto cool to room temperature
  5. temperatureThe reaction is heated
  6. temperatureto reflux over night
  7. customThe solvent is evaporated
  8. customFlash-chromatography Hexane/Ethylacetate (2:1) afforded the product

Sources & evidence

ORD record
ord-eb1284ff4830490585e2449b615bf05c
Source dataset
uspto-grants-2000_08
Patent number
US06107291

Reaction notes

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