(R)-N-((R)-1-(4-fluoro-3-methoxyphenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-2-methylpropane-2-sulfinamide → (R)-N-((4-fluoro-3-methoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methylene)-2-methylpropane-2-sulfinamide

HRID 1712838Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]([NH:30][S@@:31]([C:33]([CH3:36])([CH3:35])[CH3:34])=[O:32])([C:16]2[CH:21]=[C:20]([O:22][C:23]([F:28])([F:27])[CH:24]([F:26])[F:25])[CH:19]=[C:18]([F:29])[CH:17]=2)CC2C=CC=CC=2)=[CH:4][C:3]=1[O:37][CH3:38].F[C:40]1[CH:45]=[CH:44][C:43]([C@@:46](N[S@](C(C)(C)C)=O)(C2[CH:59]=[C:58]([O:60]C(F)(F)C(F)F)[CH:57]=C(F)C=2)CC2C=CC=CC=2)=[CH:42][C:41]=1OC>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:16]2[CH:21]=[C:20]([O:22][C:23]([F:28])([F:27])[CH:24]([F:26])[F:25])[CH:19]=[C:18]([F:29])[CH:17]=2)=[N:30][S@@:31]([C:33]([CH3:34])([CH3:35])[CH3:36])=[O:32])=[CH:4][C:3]=1[O:37][CH3:38].[CH3:44][CH2:45][CH2:40][CH2:41][CH2:42][CH2:43][CH3:46].[CH3:57][CH:58]([OH:60])[CH3:59]

Participants

Reactant 2

HCID 59458676(R)-N-((R)-1-(4-fluoro-3-methoxyphenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-2-methylpropane-2-sulfinamide

HCID 86613066(S)-N-((R)-1-(4-fluoro-3-methoxyphenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-2-methylpropane-2-sulfinamide

Product 2

HCID 21225753Isopropanol heptaneYield 68%

HCID 86612971(R)-N-((4-fluoro-3-methoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methylene)-2-methylpropane-2-sulfinamideYield 90%

Procedure

(R) —N-((4-fluoro-3-methoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methylene)-2-methylpropane-2-sulfinamide was prepared by the methods described in Procedures 5 yielding a 3:1 diastereomeric mixture of (R) —N—((R)-1-(4-fluoro-3-methoxyphenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-2-methylpropane-2-sulfinamide and (S)—N-((R)-1-(4-fluoro-3-methoxyphenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-2-methylpropane-2-sulfinamide in 90% yield. The diastereomers were separated by Chiralcel AD column chromatography elution with Heptane IPA (68% yield). Analytical data and yield for diastereomers in here. Isomer A: LCMS: [M+H] 560.2, retention time=4.08 min (Phenomenex Luna C18 5μ column, eluting with 10-90% aqueous methanol containing 0.1% TFA over a 4 minute gradient, flow rate 5 mL/min, monitoring at 220 nm); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.23 (s, 9H), 3.63 (d, J=12 Hz, 1H), 3.73 (s, 3H), 3.89 (d, J=12 Hz, 1H), 5.94 (tt, J=53, 2.4 Hz, 1H), 6.67-6.74 (m, 2H), 6.96-7.03 (m, 3H), 7.36-7.14 (m, 6H) ppm. Chiral HPLC: RT=8.21 min (Chiral AD column 4.6×250 mm; 20% Isocratic; Solvent A=Heptane, Solvent B=0.1% DEA in IPA). Isomer B: LCMS: RT=4.022 min [M+H] 560.2 (4 min Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.1% TFA; 4 mL/min, monitoring at 220 nm). 1H NMR (400 MHz, CDCl3) δ ppm 1.20 (s, 9H) 3.56 (d, J=12.09 Hz, 1H) 3.77 (s, 3H) 3.98 (d, J=12.64 Hz, 1H) 4.20 (s, 1H) 5.69-6.00 (m, 1H) 6.67-6.74 (m, 2H) 6.80-6.89 (m, 2H) 6.91 (d, J=7.70 Hz, 2H) 7.02-7.08 (m, 1H) 7.10 (s, 1H) 7.11-7.20 (m, 3H). Chiral HPLC: RT=10.34 min (Chiral AD column 4.6×250 mm; 20% Isocratic; Solvent A=Heptane, Solvent B=0.1% DEA in IPA).

Sources & evidence

ORD record: ord-5854f6036151400bab56be27ed26c0c2
Source dataset: uspto-grants-2010_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07790770B2

Reaction notes

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