Dimethyl Sulfide → (4S,5R)-5-[4-(6-Ethylaminomethyl-pyridin-3-yl)-phenyl]-4-fluoromethyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester

HRID 1487517Notes

Reaction equation

HRID 1487517 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][F:14])[C@@H:11]([C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:22]=[N:23][C:24]([C:27](=O)[NH:28][CH2:29][CH3:30])=[CH:25][CH:26]=3)=[CH:17][CH:16]=2)[O:10][C:9]1([CH3:33])[CH3:32])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(C)C=CC=CC=1.CSC>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][F:14])[C@@H:11]([C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:22]=[N:23][C:24]([CH2:27][NH:28][CH2:29][CH3:30])=[CH:25][CH:26]=3)=[CH:17][CH:16]=2)[O:10][C:9]1([CH3:32])[CH3:33])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 1068Dimethyl SulfideHCID 1140TolueneHCID 86695463(4S,5R)-5-[4-(6-Ethylcarbamoyl-pyridin-3-yl)-phenyl]-4-fluoromethyl-2,2-dimethyl-oxazolidine-3-carboxylicacid tert-butyl ester

Product 1

HCID 86695464(4S,5R)-5-[4-(6-Ethylaminomethyl-pyridin-3-yl)-phenyl]-4-fluoromethyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl esterYield 24.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To a stirred solution of (4S,5R)-5-[4-(6-Ethylcarbamoyl-pyridin-3-yl)-phenyl]-4-fluoromethyl-2,2-dimethyl-oxazolidine-3-carboxylicacid tert-butyl ester (0.21 g, 0.459 mmol) in dry tetrahydrofuran (5.25 mL) is added 2 M toluene solution of BH3.dimethylsulfide (0.104 g, 1.378 mmol) at 0° C. Reaction heated to 65° C. for 16 hours. Quenched with Methanol (2 mL). Volatiles were removed under reduced pressure to obtain crude material purified by column chromatography eluting in 6 methanol in CH2Cl2 to afford title compound (0.05 g): 1H-NMR (400 MHz, DMSO-d6): δ: 1.09 (t, 3H, J=7.15 Hz), 1.43 (s, 9H), 1.51 (s, 3H), 1.63 (s, 3H), 3.15 (m, 2H), 3.82-3.89 (m, 2H), 3.95 (s, 2H), 4.10 (m, 1H), 4.45-4.55 (m, 2H), 5.12 (d, 1H, J=7.24 Hz), 7.52 (d, 1H, J=8.20 Hz), 7.57 (d, 2H, J=8.20 Hz), 7.75 (d, 2H, J=8.24 Hz), 8.09 (dd, 1H, J=7.88 Hz, J=2.08 Hz), 8.84 (d, 1H, J=1.92 Hz). LC-MS (m/z): [M+H]=444.

Workup

  1. customat 0° C
  2. customReaction
  3. customQuenched with Methanol (2 mL)
  4. customVolatiles were removed under reduced pressure
  5. customto obtain crude material
  6. custompurified by column chromatography
  7. washeluting in 6 methanol in CH2Cl2

Sources & evidence

ORD record
ord-b5617e995ba144cfaf69ff24aa03ed92
Source dataset
uspto-grants-2016_08
Patent number
US09428528B2

Reaction notes

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