Ethylamine → HCID 67480613, compound

HRID 2273033Notes

Reaction equation

HRID 2273033 reaction equation
[CH2:1]([O:8][C@@H:9]1[C@H:14]2[NH:15][C:16](=O)[O:17][C@H:13]2[CH2:12][C@H:11]([CH2:19][O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C@H]1O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:29]([CH3:37])S(C(F)(F)F)(=O)=O.[CH2:38]([NH2:40])[CH3:39]>C(Cl)Cl>[CH2:1]([O:8][C@@H:9]1[C@H:14]2[N:15]=[C:16]([NH:40][CH2:38][CH3:39])[O:17][C@H:13]2[CH2:12][C@H:11]([CH2:19][O:20][CH2:21][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[C@H:37]1[OH:29])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6341EthylamineHCID 9526Methyl triflateHCID 67480227HCID 67480227, compound

Product 1

HCID 67480613HCID 67480613, compoundYield 18.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (3aS,4R,5R,6R,7aS)-4-(benzyloxy)-6-((benzyloxy)methyl)-5-hydroxyhexahydrobenzo[d]oxazol-2(3H)-one (Tetrahedron Lett. 1993, 34, 1525-1528) (235 mg, 0.614 mmol) in dry DCM (1.5 mL) under N2 at 0° C. was added methyl triflate (0.135 mL, 1.23 mmol) dropwise. The mixture was stirred at room temperature for 18 h. The reaction was cooled to 0° C. and ethylamine (0.40 mL, 6.14 mmol) was added. The mixture was stirred at 0° C. for 5 h. The mixture was diluted with aqueous satd. NaHCO3 (15 mL), extracted with DCM (2×15 mL). The extracts were dried (K2CO3) and concentrated to give the crude product (197 mg). This was purified by silica gel chromatography, eluted with 40-60% EtOAc in hexanes to recover the starting material (107 mg, recovery 46%). Further eluted the column with 92:6:2 DCM-MeOH—NH4OH to give the product (3aS,4R,5R,6R,7aS)-4-(benzyloxy)-6-((benzyloxy)methyl)-2-(ethylamino)-3a,4,5,6,7,7a-hexahydrobenzo[d]oxazol-5-ol (46 mg, 18%). 1H NMR (600 MHz, CDCl3) δ 7.38-7.27 (m, 10H), 4.89 (d, J=11.6, 1H), 4.72-4.69 (m, 1H), 4.69 (d, J=8.2, 1H), 4.53 (s, 2H), 3.99 (t, J=6.8, 1H), 3.61-3.54 (m, 3H), 3.46 (t, J=6.4, 1H), 3.29-3.20 (m, 2H), 2.11 (dt, J=14.8, 3.0, 1H), 1.94-1.88 (m, 1H), 1.78 (ddd, J=15.7, 12.4, 4.0, 1H), 1.18 (t, J=7.2, 3H).

Workup

  1. temperatureThe reaction was cooled to 0° C.
  2. stirringThe mixture was stirred at 0° C. for 5 h
  3. additionThe mixture was diluted with aqueous satd
  4. extractionNaHCO3 (15 mL), extracted with DCM (2×15 mL)
  5. dry with materialThe extracts were dried (K2CO3)
  6. concentrationconcentrated
  7. customto give the crude product (197 mg)
  8. customThis was purified by silica gel chromatography
  9. washeluted with 40-60% EtOAc in hexanes
  10. customto recover the starting material (107 mg, recovery 46%)
  11. washFurther eluted the column with 92:6:2 DCM-MeOH—NH4OH

Sources & evidence

ORD record
ord-f619d89ad2e544c2ab9906b82a8be3b5
Source dataset
uspto-grants-2015_09
Patent number
US09120781B2

Reaction notes

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