Potassium Carbonate → (3R,9aS)-tert-butyl 3-(3-cyano-2-cyclopropyl-4-fluorophenyl)hexahydropyrazino[2,1-c][1,4]oxazine-8(1H)-carboxylate

HRID 1502081Notes

Reaction equation

Cl[C:2]1[C:7]([C:8]#[N:9])=[C:6]([F:10])[CH:5]=[CH:4][C:3]=1[C@H:11]1[O:16][CH2:15][C@@H:14]2[CH2:17][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:19][CH2:20][N:13]2[CH2:12]1.[CH:28]1([B-](F)(F)F)[CH2:30][CH2:29]1.[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C(=O)([O-])[O-].[K+].[K+].COC1CCCC1>CC([O-])=O.CC([O-])=O.[Pd+2].O>[C:8]([C:7]1[C:2]([CH:28]2[CH2:30][CH2:29]2)=[C:3]([C@H:11]2[O:16][CH2:15][C@@H:14]3[CH2:17][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:19][CH2:20][N:13]3[CH2:12]2)[CH:4]=[CH:5][C:6]=1[F:10])#[N:9]

Participants

Conditions

Temperature: 100 °C

Procedure

To a microwave vial was charged with (3R,9aS)-tert-butyl 3-(2-chloro-3-cyano-4-fluorophenyl)hexahydropyrazino[2,1-c][1,4]oxazine-8(1H)-carboxylate (30 mg, 0.076 mmol), potassium cyclopropyltrifluoroborate (16.8 mg, 0.114 mmol), Pd(OAc)2 (1.7 mg, 7.58 μmol), X-Phos (7.2 mg, 0.015 mmol), and potassium carbonate (31.4 mg, 0.227 mmol). CPME (0.4 mL) and Water (40 μL) were added, and the reaction mixture was degassed with N2 and heated at 100° C. for 24 h. The reaction mixture was filtered to give the crude product, which was purified by prep-TLC (1000 μm, 5% MeOH/DCM) to give the title compound: LC/MS: [(M+1-56)]+=346.3.

Workup

customthe reaction mixture was degassed with N2
filtrationThe reaction mixture was filtered
customto give the crude product, which
customwas purified by prep-TLC (1000 μm, 5% MeOH/DCM)

Sources & evidence

ORD record: ord-19c7f2cb4f414f2096af8bc3b95607f2
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09206199B2

Reaction notes

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