Citric Acid → 2-(1-(Tert-butoxycarbonylamino)cyclopropyl)-2-(4-chlorophenyl)acetic acid

HRID 625075Notes

Reaction equation

HRID 625075 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:11]2([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:13][CH2:12]2)[CH:9]=[O:10])=[CH:4][CH:3]=1.CC(=CC)C.[OH:27]P([O-])(O)=O.[K+].Cl([O-])=O.[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CC(O)(C)C.O>[C:17]([O:16][C:15]([NH:14][C:11]1([CH:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[C:9]([OH:27])=[O:10])[CH2:12][CH2:13]1)=[O:21])([CH3:18])([CH3:20])[CH3:19]

Participants

8

Reactant 5

HCID 311Citric AcidHCID 105532-Methyl-2-buteneHCID 516951Monobasic potassium phosphateHCID 23668197Sodium ChloriteHCID 86675331tert-Butyl 1-(1-(4-chlorophenyl)-2-oxoethyl)cyclopropylcarbamate

Product 1

HCID 674591692-(1-(Tert-butoxycarbonylamino)cyclopropyl)-2-(4-chlorophenyl)acetic acidYield 91.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6386tert-ButanolSolvent

Procedure

tert-Butyl 1-(1-(4-chlorophenyl)-2-oxoethyl)cyclopropylcarbamate (0.64 mmol), 2-methyl-2-butene (1.6 mL, 2.0 M THF solution, 3.2 mmol) and KH2PO4 (0.087 g, 0.64 mmol) were dissolved in t-BuOH (20 mL)-water (6 mL). Sodium chlorite (0.174 g, 1.93 mmol) was added portionwise at 0° C. The mixture was stirred at room temperature for 2 hours and then acidified with 10% citric acid. The reaction was extracted with EtOAc. The combined organic layers were washed with brine, dried and concentrated to give 2-(1-(tert-butoxycarbonylamino)cyclopropyl)-2-(4-chlorophenyl)acetic acid (0.19 g, 91%) as a colorless syrup, which was used for amide coupling without further purification. LCMS: 325.8 [M+H+] (APCI+); Rf: 3.31 min.

Workup

  1. extractionThe reaction was extracted with EtOAc
  2. washThe combined organic layers were washed with brine
  3. customdried
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-b79ad6a1a8f24e7f8fa907f20162e474
Source dataset
uspto-grants-2016_04
Patent number
US09303040B2

Reaction notes

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