Diisopropylethylamine → HCID 86726816, compound

HRID 1499600Notes

Reaction equation

HRID 1499600 reaction equation
[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:19])[CH2:15][CH:16]1[CH2:18][CH2:17]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[CH:29]([C@H:31]1[CH2:35][O:34][C:33]([CH3:37])([CH3:36])[N:32]1[C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])=[O:30]>C(Cl)Cl.[Ti](Cl)(Cl)(Cl)Cl>[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:19])[C@H:15]([CH:16]1[CH2:17][CH2:18]1)[C@H:29]([C@H:31]1[CH2:35][O:34][C:33]([CH3:37])([CH3:36])[N:32]1[C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[OH:30])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 1787923-Boc-2,2-dimethyloxazolidine-4-carboxaldehyde, (R)-(+)-HCID 86726817HCID 86726817, compound

Product 1

HCID 86726816HCID 86726816, compoundYield 50.5%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-20 °C

Procedure

To a −40° C. solution of (4R)-4-benzyl-3-(cyclopropylacetyl)-1,3-oxazolidin-2-one (2.0 g, 7.7 mmol) in anhydrous DCM (45 mL), a solution of 1.0 M titanium tetrachloride in DCM (9.3 mL) was added drop-wise under an atmosphere of nitrogen to form a yellow slurry. After 10 min., DIPEA (3.36 mL, 19.3 mmol) was added drop-wise, changing the color from yellow to deep purple. The reaction mixture was allowed to warm gradually to −20° C. while stirring over 1 h. The reaction mixture was again cooled to −40° C., and a solution of tert-butyl (4R)-4-formyl-2,2-dimethyl-1,3-oxazolidine-3-carboxylate (1.8 g, 7.85 mmol) (Aldrich) in anhydrous DCM (5 mL) was added drop-wise. The reaction mixture was allowed to warm gradually to 0° C. over 1 h and then allowed to stir for an additional 1.5 h at 0° C. The reaction was quenched by the addition of saturated NH4Cl (aq.) (15 mL). After separation of the two layers that resulted, the organic layer was washed with water and brine, dried over Na2SO4, concentrated under reduced pressure and purified by flash chromatography (120 g silica gel, eluting with 0-60% EtOAc/hexanes) to afford the sub-title compound (1.9 g, 50%). LC/MS (ESI) m/z calc. for C26H36N2O7Na: 511.2 [M+Na]+. found 511.1.

Workup

  1. customto form a yellow slurry
  2. temperatureThe reaction mixture was again cooled to −40° C.
  3. temperatureto warm gradually to 0° C. over 1 h
  4. stirringto stir for an additional 1.5 h at 0° C
  5. customThe reaction was quenched by the addition of saturated NH4Cl (aq.) (15 mL)
  6. customAfter separation of the two layers
  7. customthat resulted
  8. washthe organic layer was washed with water and brine
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated under reduced pressure
  11. custompurified by flash chromatography (120 g silica gel, eluting with 0-60% EtOAc/hexanes)

Sources & evidence

ORD record
ord-af9c06bd79db42388c4e3907ced953f2
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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