HCID 22135323, compound → HCID 57929708, compound

HRID 1012868Notes

Reaction equation

HRID 1012868 reaction equation
[Si:1]([O:8][CH2:9][C@H:10]1[CH2:15][CH2:14][O:13][C:12](=[O:16])[NH:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].I[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24]([O:26][CH:27]([CH3:29])[CH3:28])=[O:25]>CN(C=O)C.O.CCOCC>[OH:8][CH2:9][C@H:10]1[CH2:15][CH2:14][O:13][C:12](=[O:16])[N:11]1[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24]([O:26][CH:27]([CH3:28])[CH3:29])=[O:25].[Si:1]([O:8][CH2:9][C@H:10]1[CH2:15][CH2:14][O:13][C:12](=[O:16])[N:11]1[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24]([O:26][CH:27]([CH3:28])[CH3:29])=[O:25])([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

Participants

6

Reactant 2

HCID 22135323HCID 22135323, compoundHCID 58635315HCID 58635315, compound

Product 2

HCID 57929708HCID 57929708, compoundHCID 67318482HCID 67318482, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21584184Diethylether waterSolvent

Procedure

To a solution of (4R)-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1,3-oxazinan-2-one (0.51 g, 2.078 mmol) in DMF (10 mL) at rt under N2 was added KHMDS (0.5 M in toluene, 5 mL) dropwise (gel like precipitation formation) and the mixture was stirred for 10 min. Isopropyl 7-iodoheptanoate (1.24 g, 4.16 mmol, 2 eq) was then added in one portion and the mixture stirred at 65° C. for an additional 5 h and cooled to rt, diluted with water/ether. The layers were separated and the aqueous layer extracted with ether. The organic layers were combined, washed with water and brine, dried over MgSO4 and filtered. The filtrate was concentrated in vacuo and the residue purified by column chromatography (15-30% acetone/toluene) to give desired product isopropyl 7-[(4R)-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-oxo-1,3-oxazinan-3-yl]heptanoate as a colorless oil. 1H NMR (400 MHz, Acetone-d6): δ4.98-4.90 (1 H, m), 4.38-4.30 (1 H, m), 4.16-4.12 (1 H, m), 3.83-3.77 (2 H, m), 3.56-3.48 (2 H, m), 3.15-3.07 (1 H, m), 2.26 (2 H, t), 2.11-2.09 (2 H, m), 1.69-1.53 (4 H, m), 1.41-1.27 (4 H, m), 1.21 (6 H, d), 0.92 (9 H, s), 0.12 (6 H, s).

Workup

  1. customKHMDS (0.5 M in toluene, 5 mL) dropwise (gel like precipitation formation)
  2. stirringthe mixture stirred at 65° C. for an additional 5 h
  3. customThe layers were separated
  4. extractionthe aqueous layer extracted with ether
  5. washwashed with water and brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo
  9. customthe residue purified by column chromatography (15-30% acetone/toluene)

Sources & evidence

ORD record
ord-f61b8c8e1c8a4bc780c0c18e16f47942
Source dataset
uspto-grants-2011_07
Patent number
USRE042562E1

Reaction notes

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