Sodium Bicarbonate → (S)-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(4-(5-(2-hydroxypropan-2-yl)pyrimidin-2-yl)phenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one

HRID 1046099Notes

Reaction equation

HRID 1046099 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]([OH:11])([CH3:10])[CH3:9])=[CH:4][N:3]=1.[OH:12][C:13]([CH3:46])([CH3:45])[CH2:14][C@@:15]1([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[O:20][C:19](=[O:21])[N:18]([C@H:22]([C:24]2[CH:29]=[CH:28][C:27](B3OC(C)(C)C(C)(C)O3)=[CH:26][CH:25]=2)[CH3:23])[CH2:17][CH2:16]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:12][C:13]([CH3:45])([CH3:46])[CH2:14][C@@:15]1([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[O:20][C:19](=[O:21])[N:18]([C@H:22]([C:24]2[CH:25]=[CH:26][C:27]([C:2]3[N:7]=[CH:6][C:5]([C:8]([OH:11])([CH3:10])[CH3:9])=[CH:4][N:3]=3)=[CH:28][CH:29]=2)[CH3:23])[CH2:17][CH2:16]1

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 137157472-(2-Chloropyrimidin-5-yl)propan-2-olHCID 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-one

Product 1

HCID 58485304(S)-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(4-(5-(2-hydroxypropan-2-yl)pyrimidin-2-yl)phenyl)ethyl)-6-phenyl-1,3-oxazinan-2-oneYield 34.3%

Reagents, catalysts & solvents 3

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

Procedure

To a solution of 2-(2-chloropyrimidin-5-yl)propan-2-ol (30 mg, 0.17 mmol) in DME (6 mL) was added Pd(PPh3)4 (10 mg, 0.01 mmol) under nitrogen. The mixture was stirred at room temperature for 1 hour. (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 (60 mg, 0.125 mmol) in EtOH (2 mL) was added, followed by addition of satd aq NaHCO3 (2 mL). The mixture was stirred at 100° C. for 2 h. The reaction was quenched with water, and extracted with EtOAc. The combined organic layer was dried over anhydrous Na2SO4 and concentrated to give (S)-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(4-(5-(2-hydroxypropan-2-yl)pyrimidin-2-yl)phenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one (21 mg, yield 25%). LC-MS Method 2 tR=0.98 min, m/z=512, 490, 472, 432; 1H NMR (CD3OD): δ 1.02 (s, 3H), 1.13 (s, 3H), 1.50 (d, 3H), 1.61 (s, 6H), 2.02 (s, 1H), 2.18 (m, 5H), 2.30 (m, 1H), 2.75 (m, 1H), 5.66 (m, 1H), 7.00 (m, 2H), 7.20-7.33 (m, 5H), 8.10 (m, 2H), 8.92 (s, 2H).

Workup

  1. stirringThe mixture was stirred at 100° C. for 2 h
  2. customThe reaction was quenched with water
  3. extractionextracted with EtOAc
  4. dry with materialThe combined organic layer was dried over anhydrous Na2SO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-1a1ca5ef91d948c7a1deb8b52a29f2d0
Source dataset
uspto-grants-2013_10
Patent number
US08569292B2

Reaction notes

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