Potassium Phosphate, Tribasic → HCID 58109645, compound

HRID 2037441Notes

Reaction equation

[CH2:1]([C@@:4]1([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16](Br)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1)[CH:2]=[CH2:3].[CH:27]1(B(O)O)[CH2:29][CH2:28]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2].CN(C=O)C.O>[CH2:1]([C@@:4]1([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([CH:27]3[CH2:29][CH2:28]3)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1)[CH:2]=[CH2:3]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of (R)-6-allyl-3-((S)-1-(4-bromophenyl)ethyl)-6-(4-fluorophenyl)-1,3-oxazinan-2-one (15 mg, 0.036 mmol), cyclopropylboronic acid (5.5 mg, 1.78 equiv.), Pd(OAc)2 (2 mg, 25% mol), tricyclohexylphosphine (5 mg, 50% mol), K3PO4 (20 mg, excess), water (1 mL) and DMF (1 mL) were heated in a microwave oven for 45 min at 100° C. The mixture was diluted with EtOAc (10 mL), washed with water (4 mL) and brine (5 mL), and dried over Na2SO4. After filtration and concentration, the residue was purified by preparative HPLC to afford (R)-6-allyl-3-((S)-1-(4-cyclopropylphenyl)ethyl)-6-(4-fluorophenyl)-1,3-oxazinan-2-one (6.2 mg, 45%). LC-MS Method 1, tR=2.02 min, m/z=380. 1H NMR (CDCl3) 7.24 (m, 2H), 7.02 (t, 2H), 6.76 (q, 4H), 5.75-5.56 (m, 2H), 5.10-4.98 (dd, 2H), 2.57 (m, 2H), 1.48 (d, 3H), 0.92 (m, 2H), 0.60 (m, 2H).

Workup

washwashed with water (4 mL) and brine (5 mL)
dry with materialdried over Na2SO4
filtrationAfter filtration and concentration
customthe residue was purified by preparative HPLC

Sources & evidence

ORD record: ord-e1f6c579b10347e893b0bcbb8718509e
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08575156B2

Reaction notes

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