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

HRID 537998Notes

Reaction equation

HRID 537998 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.[CH3:34][O:35][C:36]1[CH:41]=[CH:40][C:39]([C:42]([CH3:46])([CH3:45])[CH2:43][OH:44])=[CH:38][C:37]=1B1OC(C)(C)C(C)(C)O1.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:37]3[CH:38]=[C:39]([C:42]([CH3:46])([CH3:45])[CH2:43][OH:44])[CH:40]=[CH:41][C:36]=3[O:35][CH3:34])[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 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×HCID 575443992-[4-Methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-methylpropan-1-ol2×

Product 1

HCID 24739924(4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-3-({6-[5-(2-hydroxy-1,1-dimethylethyl)-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; 30 mg; 0.052 mmol) was treated with 2-[4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-methylpropan-1-ol (Intermediate 26; 20 mg; 0.067 mmol), 1-1′-bis(di tert-butylphosphino)ferrocene palladium dichloride (3.4 mg; 0.0052 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-(2-hydroxy-1,1-dimethylethyl)-2-methoxyphenyl]-2,3-dihydro-1H-inden-5-yl}methyl)-4-methyl-1,3-oxazinan-2-one as a clear glass. LCMS=636.1 (M+1)+. 1H NMR (CDCl3, 500 MHz, mixture of atropisomers): δ 7.84-7.79 (m, 2H), 7.75 (s, 1H), 7.33 (dd, J=8.7, 2.5 Hz, 1H), 7.29 (s, 1H), 7.23 (d, J=2.3 Hz, 1H), 7.13 (s, 1H), 6.95-6.92 (m, 1H), 5.41 (d, J=15.3 Hz, 1H), 4.93 (d, J=10.5 Hz, 1H), 3.93 (d, J=15.4 Hz, 1H), 3.81 (s, 3H), 3.65-3.61 (m, 1H), 3.57-3.54 (m, 1H), 3.44-3.36 (m, 1H), 2.99-2.94 (m, 4H), 2.20-2.10 (m, 3H), 1.76-1.64 (m, 1H), 1.33-1.25 (m, 6H), 1.05-1.02 (m, 3H).

Sources & evidence

ORD record
ord-8091d0709a7f4382974f12c20335cbdf
Source dataset
uspto-grants-2014_10
Patent number
US08865707B2

Reaction notes

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