Propargyl alcohol → (R)-Methyl 2-Acetamido-3-(prop-2-ynyloxy)propanoate

HRID 1425690Notes

Reaction equation

HRID 1425690 reaction equation
[C:1]([N@@:4]1[CH2:6][CH:5]1[C:7]([O:9][CH3:10])=[O:8])(=[O:3])[CH3:2].[CH2:11]([OH:14])[C:12]#[CH:13].B(F)(F)F.CCOCC>C(Cl)Cl>[C:1]([NH:4][C@H:5]([CH2:6][O:14][CH2:11][C:12]#[CH:13])[C:7]([O:9][CH3:10])=[O:8])(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 7859Propargyl alcoholHCID 8000Boron trifluoride etherateHCID 21609344Methyl 1-acetylaziridine-2-carboxylate

Product 1

HCID 44542972(R)-Methyl 2-Acetamido-3-(prop-2-ynyloxy)propanoateYield 68.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-20 °C

Procedure

(R)-Methyl 1-acetylaziridine-2-carboxylate (1.50 g, 10.49 mmol) was dissolved in CH2Cl2 (40 mL) and cooled to −20° C. under Ar, and then propargyl alcohol (0.92 mL, 15.74 mmol) was added. After the solution was stirred (2 min), BF3.Et2O (1.39 mL, 11.01 mmol) was added dropwise. The reaction mixture was allowed to stir at room temperature (2-3 h) and then washed with saturated aqueous NaHCO3 (30 mL) and saturated aqueous brine (30 mL). The organic layer was dried (Na2SO4) and evaporated in vacuo, and then the crude product was purified by column chromatography (SiO2; 3/1 EtOAc/hexanes) and crystallized (cold hexanes) to yield 1.43 g (68%) of desired product as a white solid: mp 58.5-59.5° C.; [α]25D −64.6° (c 1, CHCl3); Rf=0.35 (3/1 EtOAc/hexanes); IR (nujol mull) 3301, 2919, 2114, 1750, 1639, 1542, 1457 cm−1; 1H NMR (CDCl3) δ 2.06 (s, CH3C(O)), 2.46 (t, J=2.3 Hz, CH2CCH), 3.78 (s, OCH3), 3.79 (dd, J=3.3, 9.6 Hz, CHH′OCH2), 3.98 (dd, J=2.9, 9.6 Hz, CHH′OCH2), 4.09-4.21 (m, OCH2C), 4.77-4.82 (m, CH), 6.33-6.35 (br d, J=7.2 Hz, NHCH); 13C NMR (CDCl3) δ 23.3 (CH3C(O)), 52.6 (CH), 52.8 (OCH3), 58.7 (CH2CCH), 69.6 (CH2OCH2), 75.3 (CH2CCH), 79.0 (CH2CCH), 170.1, 170.8 (2 C(O)); HRMS (ESI) 200.0916 [M+H+] (calcd. for C9H14NO4 200.0923); Anal. (C9H13NO4) Calcd.: C, 54.26%; H, 6.58%; N, 7.03%. Found: C, 54.30%; H, 6.66%; N, 6.89%.

Workup

  1. additionwas added dropwise
  2. washwashed with saturated aqueous NaHCO3 (30 mL) and saturated aqueous brine (30 mL)
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. customevaporated in vacuo
  5. customthe crude product was purified by column chromatography (SiO2; 3/1 EtOAc/hexanes)
  6. customcrystallized (cold hexanes)

Sources & evidence

ORD record
ord-8ff2636221dd4918b22372836e93030e
Source dataset
uspto-grants-2015_01
Patent number
US08933065B2

Reaction notes

Loading…