Ethanimidic acid, methyl ester, hydrochloride (1:1) → HCID 67480743, compound

HRID 2273037Notes

Reaction equation

HRID 2273037 reaction equation
[NH2:1][CH:2]1[CH:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:6]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:5]([CH2:24][O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:4][CH:3]1[OH:33].Cl.[C:35](=N)(OC)[CH3:36]>C(Cl)Cl>[CH2:9]([O:8][CH:7]1[CH:2]2[N:1]=[C:35]([CH3:36])[O:33][CH:3]2[CH2:4][CH:5]([CH2:24][O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:6]1[O:16][CH2:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

4

Reactant 2

HCID 10313100Ethanimidic acid, methyl ester, hydrochloride (1:1)HCID 67480625HCID 67480625, compound

Product 1

HCID 67480743HCID 67480743, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of Intermediate B (224 mg, 0.50 mmol) in dry DCM (2 mL) was added methyl acetimidate hydrochloride (110 mg, 1.00 mmol) followed by a solution of TEA (51 mg, 0.50 mmol) in dry DCM (2 mL). The mixture was stirred under nitrogen at room temperature for 3 h. The mixture was diluted with satd. aqueous NaHCO3 (10 mL), extracted with DCM (3×10 mL). The combined extracts were washed with brine and dried over Na2SO4. Solvents were evaporated under reduced pressure. The crude product was purified by silica gel column chromatography, eluted with 40% EtOAc in hexanes to give the product rac-(3aS,4R,5R,6R,7aS)-4,5-bis(benzyloxy)-6-((benzyloxy)methyl)-2-methyl-3a,4,5,6,7,7a-hexahydrobenzo[d]oxazole (105 mg, 45%) as a syrup. 1H NMR (400 MHz, CDCl3) δ 7.39-7.25 (m, 15H), 4.86 (d, J=11.6 Hz, 1H), 4.77 (d, J=11.3 Hz, 1H), 4.71 (m, 1H), 4.68 (d, J=11.3 Hz, 1H), 4.47-4.41 (m, 3H), 4.17-4.12 (m, 1H), 3.64 (t, J=5.8 Hz, 1H), 3.56 (dd, J=9.0, 4.4 Hz, 1H), 3.51 (dd, J=8.6, 6.3 Hz, 1H), 3.47 (dd, J=9.1, 2.8 Hz, 1H), 2.14-2.08 (m, 1H), 1.98 (s, 3H), 1.93-1.85 (m, 2H).

Workup

  1. additionThe mixture was diluted with satd
  2. extractionaqueous NaHCO3 (10 mL), extracted with DCM (3×10 mL)
  3. washThe combined extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. customSolvents were evaporated under reduced pressure
  6. customThe crude product was purified by silica gel column chromatography
  7. washeluted with 40% EtOAc in hexanes

Sources & evidence

ORD record
ord-b2fad0fee6bd4f4fa57b914dbc6ed8d6
Source dataset
uspto-grants-2015_09
Patent number
US09120781B2

Reaction notes

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