Potassium Carbonate → (4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-3-{[5'-[1-(hydroxymethyl)cyclopropyl]-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazinan-2-one

HRID 537999Notes

Reaction equation

HRID 537999 reaction equation
[F:1][C:2]([F:34])([F:33])[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:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[CH:23][C:22]=3I)[C@@H:15]([CH3:32])[CH2:14]2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:35][O:36][C:37]1[CH:42]=[CH:41][C:40]([C:43]2([CH2:46][OH:47])[CH2:45][CH2:44]2)=[CH:39][C:38]=1B1OC(C)(C)C(C)(C)O1.C([O-])([O-])=O.[K+].[K+]>C1COCC1>[F:1][C:2]([F:34])([F:33])[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:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[CH:23][C:22]=3[C:38]3[CH:39]=[C:40]([C:43]4([CH2:46][OH:47])[CH2:44][CH2:45]4)[CH:41]=[CH:42][C:37]=3[O:36][CH3:35])[C@@H:15]([CH3:32])[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 57544352(4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-3-[2-iodo-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazinan-2-one2×HCID 57544377{1-[4-Methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclopropyl}methanol2×

Product 1

HCID 24739925(4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-3-{[5'-[1-(hydroxymethyl)cyclopropyl]-2'-methoxy-4-(trifluoromethyl)biphenyl-2-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-[2-iodo-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazinan-2-one (Intermediate 23; 28 mg; 0.046 mmol) was treated with {1-[4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclopropyl}methanol (Intermediate 28; 18 mg; 0.060 mmol), 1-1′-bis(di tert-butylphosphino) ferrocene palladium dichloride (3.0 mg; 0.0046 mmol), 1 N K2CO3 (2 mL) and THF (2 mL) as described in Example 38 to afford (4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-3-{[5′-[1-(hydroxymethyl)cyclopropyl]-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazinan-2-one as a white solid. LCMS=662.0 (M+1)+. 1H NMR (CDCl3, 500 MHz, mixture of atropisomers): δ 7.86-7.82 (m, 2H), 7.76 (s, 1H), 7.66-7.61 (m, 2H), 7.40-7.37 (m, 1H), 7.27-7.24 (m, 2H), 6.96-6.93 (m, 1H), 5.40 (d, J=15.6 Hz, 1H), 4.91 (d, J=10.5 Hz, 1H), 4.11 (d, J=15.6 Hz, 1H), 3.91 (s, 3H), 3.68-3.56 (m, 2H), 3.39-3.32 (m, 1H), 2.24-2.16 (m, 1H), 1.80-1.64 (m, 1H), 1.05 (d, J=6.2 Hz, 3H), 0.88-0.74 (m, 4H).

Sources & evidence

ORD record
ord-4254d00af3ab4ad28e19955353c6f4bb
Source dataset
uspto-grants-2014_10
Patent number
US08865707B2

Reaction notes

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