Sodium Carbonate → HCID 117600815, compound

HRID 931661Notes

Reaction equation

HRID 931661 reaction equation
[O:1]1[CH2:6][CH:5]=C(B2OC(C)(C)C(C)(C)O2)[CH2:3][CH2:2]1.FC(F)(F)S(O[C:22]1[CH:35]=[C:34]2[C:25]([O:26][C:27]3[CH:28]=[CH:29][C:30]([NH2:42])=[CH:31][C:32]=3[C@:33]32[CH2:40][CH2:39][O:38][C:37]([NH2:41])=[N:36]3)=[C:24]([F:43])[CH:23]=1)(=O)=O.[C:46](=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[O:1]1[CH2:6][CH:5]=[C:23]([C:22]2[CH:46]=[C:24]([F:43])[C:25]3[O:26][C:27]4[C:32](=[CH:31][C:30]([NH2:42])=[CH:29][CH:28]=4)[C@@:33]4([CH2:40][CH2:39][O:38][C:37]([NH2:41])=[N:36]4)[C:34]=3[CH:35]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 117600820HCID 117600820, compound

Product 1

HCID 117600815HCID 117600815, compoundYield 27.2%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
85 °C

Procedure

In a microwave vial, 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.107 g, 0.509 mmol) and Pd(PPh3)4 (0.053 g, 0.046 mmol) were loaded. A solution of (S)-2,2′-diamino-5′-fluoro-5,6-dihydrospiro[[1,3]oxazine-4,9′-xanthen]-7′-yl trifluoromethanesulfonate (0.207 g, 0.463 mmol) in dmf (3.7 mL) was added via cannula. Aqueous 1.5 M sodium carbonate (0.925 mL, 1.388 mmol) was added. Argon was blown through the vessel, which was sealed and heated in an 85° C. oil bath. After 4 h, the reaction was concentrated. The residue was taken up in EtOAc (100 mL) and the organic layer was extracted with quarter-saturated brine (2×8 mL), half-saturated brine (8 mL), and saturated brine (8 mL), dried over MgSO4 and concentrated. The material was purified through silica gel (35 mL) which had been deactivated with Et3N (3.5 mL), using a gradient of 3% to 6% MeOH-dcm with 0.5% v/v Et3N, affording (S)-2′-(3,6-dihydro-2H-pyran-4-yl)-4′-fluoro-5,6-dihydrospiro[[1,3]oxazine-4,9′-xanthene]-2,7′-diamine (48 mg, 0.126 mmol). MS m/z=382 [M+H]1.

Workup

  1. customwas sealed
  2. concentrationthe reaction was concentrated
  3. extractionthe organic layer was extracted with quarter-saturated brine (2×8 mL), half-saturated brine (8 mL), and saturated brine (8 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe material was purified through silica gel (35 mL) which

Sources & evidence

ORD record
ord-cc5b330bf6564829a9f7001d623e0cb9
Source dataset
uspto-grants-2016_03
Patent number
US09296759B2

Reaction notes

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