Sodium Bicarbonate → HCID 58102384, compound

HRID 470555Notes

Reaction equation

HRID 470555 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5](=[O:13])[N:6]([CH2:8][C:9]([OH:12])([CH3:11])[CH3:10])[CH:7]=1.[OH:14][C:15]([CH3:48])([CH3:47])[CH2:16][C@@:17]1([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[O:22][C:21](=[O:23])[N:20]([C@H:24]([C:26]2[CH:31]=[CH:30][C:29](B3OC(C)(C)C(C)(C)O3)=[CH:28][CH:27]=2)[CH3:25])[CH2:19][CH2:18]1.C([O-])(O)=O.[Na+]>COCCOC.CCO.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>[OH:14][C:15]([CH3:47])([CH3:48])[CH2:16][C@@:17]1([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[O:22][C:21](=[O:23])[N:20]([C@H:24]([C:26]2[CH:27]=[CH:28][C:29]([C:2]3[CH:3]=[CH:4][C:5](=[O:13])[N:6]([CH2:8][C:9]([OH:12])([CH3:11])[CH3:10])[CH:7]=3)=[CH:30][CH:31]=2)[CH3:25])[CH2:19][CH2:18]1

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 59532385(S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-oneHCID 596357485-Bromo-1-(2-hydroxy-2-methylpropyl)-2(1H)-pyridinone

Product 1

HCID 58102384HCID 58102384, compoundYield 15.5%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of 5-bromo-1-(2-hydroxy-2-methylpropyl)pyridin-2(1H)-one (20 mg, 81.3 mmol) in DME (6 mL) was added Pd(PPh3)4 (10 mg) under nitrogen. The mixture was stirred for 1 h at rt, and a solution of (S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one (38.95 mg, 81.3 mmol) in EtOH (2 mL) and satd aq NaHCO3 (2 mL) were added. The resulting mixture was stirred at 100° C. for 2 h, quenched with water, and extracted with EtOAc. The combined organic layer was dried over anhydrous Na2SO4 and concentrated to give the crude product, which was purified by preparative TLC and preparative HPLC to afford (S)-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(4-(1-(2-hydroxy-2-methylpropyl)-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one (6.5 mg, 15.5%). LC-MS Method 2 tR=0.99 min, m/z=519; 1H NMR (CDCl3): δ 7.60-7.57 (d, 1H), 7.43 (s, 1H), 7.36-7.26 (m, 5H), 7.15 (d, 2H), 7.01 (d, 2H), 6.70 (d, 1H), 2.85 (m, 1H), 5.69-5.66 (m, 1H), 4.13-4.09 (s, 2H), 4.05-3.98 (s, 1H), 2.89-2.86 (m, 1H), 2.44-2.36 (m, 1H), 2.28-2.16 (m, 5H), 1.58-1.53 (d, 3H), 1.33-1.30 (s, 6H), 1.19 (s, 3H), 1.12 (s, 3H).

Workup

  1. additionwere added
  2. stirringThe resulting mixture was stirred at 100° C. for 2 h
  3. customquenched with water
  4. extractionextracted with EtOAc
  5. dry with materialThe combined organic layer was dried over anhydrous Na2SO4
  6. concentrationconcentrated
  7. customto give the crude product, which
  8. customwas purified by preparative TLC and preparative HPLC

Sources & evidence

ORD record
ord-7eecc477a1d048d1b02862ac38715773
Source dataset
uspto-grants-2014_01
Patent number
US08629138B2

Reaction notes

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