Potassium Carbonate → (4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-3-{[6-(5-tert-butyl-2-methoxyphenyl)-2,3-dihydro-1H-inden-5-yl]methyl}-4-methyl-1,3-oxazinan-2-one

HRID 537996Notes

Reaction equation

HRID 537996 reaction equation
[F:1][C:2]([F:33])([F:32])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:18][C:17](=[O:19])[N:16]([CH2:20][C:21]3[CH:22]=[C:23]4[C:27](=[CH:28][C:29]=3I)[CH2:26][CH2:25][CH2:24]4)[C@@H:15]([CH3:31])[CH2:14]2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[C:34]([C:38]1[CH:39]=[CH:40][C:41]([O:47][CH3:48])=[C:42](B(O)O)[CH:43]=1)([CH3:37])([CH3:36])[CH3:35].C([O-])([O-])=O.[K+].[K+]>C1COCC1>[F:1][C:2]([F:33])([F:32])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:18][C:17](=[O:19])[N:16]([CH2:20][C:21]3[CH:22]=[C:23]4[C:27](=[CH:28][C:29]=3[C:42]3[CH:43]=[C:38]([C:34]([CH3:35])([CH3:37])[CH3:36])[CH:39]=[CH:40][C:41]=3[O:47][CH3:48])[CH2:26][CH2:25][CH2:24]4)[C@@H:15]([CH3:31])[CH2:14]2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 147405795-(tert-Butyl)-2-methoxybenzeneboronic acidHCID 57544368(4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-3-[(6-iodo-2,3-dihydro-1H-inden-5-yl)methyl]-4-methyl-1,3-oxazinan-2-one2×

Product 1

HCID 24739922(4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-3-{[6-(5-tert-butyl-2-methoxyphenyl)-2,3-dihydro-1H-inden-5-yl]methyl}-4-methyl-1,3-oxazinan-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-3-[(6-iodo-2,3-dihydro-1H-inden-5-yl)methyl]-4-methyl-1,3-oxazinan-2-one (Intermediate 25; 25 mg; 0.043 mmol) was treated with (5-tert-butyl-2-methoxyphenyl)boronic acid (11.6 mg; 0.056 mmol), 1-1′-bis(di tert-butylphosphino)ferrocene palladium dichloride (2.8 mg; 0.0043 mmol), 1 N K2CO3 (1.2 mL) and THF (1.2 mL) as described in Example 38 to afford (4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-3-{[6-(5-tert-butyl-2-methoxyphenyl)-2,3-dihydro-1H-inden-5-yl]methyl}-4-methyl-1,3-oxazinan-2-one as a clear glass. LCMS=620.1 (M+1)+. 1H NMR (CDCl3, 500 MHz, mixture of atropisomers): δ 7.84-7.82 (m, 2H), 7.75 (s, 1H), 7.36 (dd, J=8.5, 2.6 Hz, 1H), 7.31 (s, 1H), 7.22 (d, J=2.5 Hz, 1H), 7.12 (s, 1H), 6.91 (d, J=8.7 Hz, 1H), 5.22 (d, J=15.4 Hz, 1H), 5.13 (d, J=10.3 Hz, 1H), 4.22 (d, J=15.5 Hz, 1H), 3.81 (s, 3H), 3.41-3.32 (m, 1H), 2.99-2.93 (m, 4H), 2.24-2.20 (m, 1H), 2.16-2.11 (m, 2H), 1.82-1.75 (m, 1H), 1.31 (s, 9H), 1.02 (d, J=6.1 Hz, 3H).

Sources & evidence

ORD record
ord-1df97b8ce5344fe191a2d92b315ec96a
Source dataset
uspto-grants-2014_10
Patent number
US08865707B2

Reaction notes

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