Diethyl Ether → (2R)-2-Amino-4-(7-hydroxy-2-oxo-2H-1-benzopyran-4-yl)butanoic acid

HRID 215699Notes

Reaction equation

HRID 215699 reaction equation
C([O:3][C:4](=O)[CH2:5][C:6](=O)[CH2:7][CH2:8][C@H:9]([NH:20]C(OCC1C=CC=CC=1)=O)[C:10]([O:12]CC1C=CC=CC=1)=[O:11])C.[C:33]1([CH:40]=[CH:39][CH:38]=[C:36]([OH:37])[CH:35]=1)[OH:34].CCOCC.C(O)(C(F)(F)F)=O>CS(O)(=O)=O.O.CC#N>[CH:40]1[C:33]([OH:34])=[CH:35][C:36]2[O:37][C:4]([CH:5]=[C:6]([CH2:7][CH2:8][C@@H:9]([NH2:20])[C:10]([OH:12])=[O:11])[C:38]=2[CH:39]=1)=[O:3]

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 5054ResorcinolHCID 6422Trifluoroacetic acidHCID 11339684(2S)-2 Benzyloxycarbonylamino-5-oxo-heptanedioic acid 1-benzyl ester 7-ethyl ester

Product 1

HCID 53487799(2R)-2-Amino-4-(7-hydroxy-2-oxo-2H-1-benzopyran-4-yl)butanoic acidYield 50%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6395Methanesulfonic AcidSolvent

Procedure

(2S)-2 Benzyloxycarbonylamino-5-oxo-heptanedioic acid 1-benzyl ester 7-ethyl ester from the previous step (2.35 g, 5 mmol) was added slowly to resorcinol (3 g, 25 mmol) in methanesulfonic acid (20 ml) and stirred for two hours at room temperature. Five volumes of ether were then added to the mixture and was cooled to −30° C. The precipitate was washed with cold ether, dissolved in water, filtered, and lyophilized. L-(7-hydroxycoumarin-4-yl)ethylglycine was purified by reverse phase HPLC to afford a brown solid in 50% yield (YMC AA12S052503WT column, 12 ml/min flow rate, from 10% to 90% CH3CN, 0.1% TFA (w/v) in water, over the course of 12 min). 1H-NMR (DMSO): δ 2.06 (s, 2H), 2.70-2.90 (m, 2H), 3.82-4.0 (m, 1H), 6.06 (s, 1H), 6.75 (dd, J=8.8, 2.4, 1H), 6.82 (d, J=2.4, 1H), 7.62 (d, J=8.8, 1H), 8.17 (s, 3H). LC-MS (ESI) calc. for C13H14NO5 (M+H+) 264.08 Da, obsd. 264.0 Da.

Workup

  1. temperaturewas cooled to −30° C
  2. washThe precipitate was washed with cold ether
  3. dissolutiondissolved in water
  4. filtrationfiltered
  5. customL-(7-hydroxycoumarin-4-yl)ethylglycine was purified by reverse phase HPLC
  6. customto afford a brown solid in 50% yield (YMC AA12S052503WT column, 12 ml/min flow rate
  7. customover the course of 12 min

Sources & evidence

ORD record
ord-284888904ee542a7a965ddd2261c7e47
Source dataset
uspto-grants-2012_06
Patent number
US08192952B2

Reaction notes

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