Allyl chloroformate → HCID 6709788, compound

HRID 1008244Notes

Reaction equation

HRID 1008244 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:15])[C@H:5]([CH2:7][C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=1)[NH2:6].C(N(C(C)C)CC)(C)C.[CH2:25]([O:28][C:29](Cl)=[O:30])[CH:26]=[CH2:27].[Cl-].[NH4+]>C1COCC1.C(Cl)Cl>[CH3:2][O:3][C:4](=[O:15])[C@@H:5]([NH:6][C:29]([O:28][CH2:25][CH:26]=[CH2:27])=[O:30])[CH2:7][C:8]1[CH:9]=[CH:10][C:11]([OH:14])=[CH:12][CH:13]=1

Participants

7

Reactant 4

HCID 18052Allyl chloroformateHCID 25517Ammonium ChlorideHCID 76956Methyl tyrosinate hydrochlorideHCID 81531Diisopropylethylamine

Product 1

HCID 6709788HCID 6709788, compoundYield 99.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of L-Tyrosine methyl ester hydrochloride (25 g, 107.9 mmol, 1.0 equiv) in THF (500 mL) and CH2Cl2 (250 mL) at room temperature was added diisopropyl ethylamine (56.5 ml, 322.5 mmol, 3.0 equiv). The solution was cooled to 0° C. and allylchoroformate (11.5 ml, 107.9 mmol, 1.0 equiv) was added dropwise. The reaction was stirred at 0° C. for 1.5 hours, after which time saturated ammonium chloride (100 mL) was added and the THF and CH2Cl2 were removed under reduced pressure. The aqueous suspension was extracted with ether (4×300 mL). The organics were combined, washed with brine, dried over MgSO4, and concentrated. Purification by flash chromatography (15→60% EtOAc/hexane) afforded 18 (30 g, 96%) as a white solid. Rf=0.43 (50% EtOAc/hexane); FTIR (neat, cm−1) 3297, 2959, 1734, 1688, 1566, 1518, 1441, 1229; 1H NMR (400 MHz, CDCl3) δ6.95 (d, J=7.9 Hz, 2H), 6.71 (d, J=8.0 Hz, 2H), 5.85 (m, 1H), 5.24 (m, 3H), 4.6 (m, 1H), 4.53 (d, J=5.2, 2H), 3.71 (s, 3H), 3.01 (m, 2H); 13C NMR (100 MHz, CDCl3) δ172.3, 155.8, 155.2, 132.3, 130.3, 127.0, 118.0, 115.5, 66.0, 54.9, 52.9, 52.4, 37.4; HRMS (ES+) calculated for C14H17NO5 (M+H)+: 280.1107, found: 280.1195.

Workup

  1. customthe THF and CH2Cl2 were removed under reduced pressure
  2. extractionThe aqueous suspension was extracted with ether (4×300 mL)
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customPurification by flash chromatography (15→60% EtOAc/hexane)

Sources & evidence

ORD record
ord-f500eb01646c4e8ba0ebb8c84be12c40
Source dataset
uspto-grants-2004_09
Patent number
US06797819B1

Reaction notes

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