Isopropanol → tert-butyl ((1S,2R,3R,5S)-5-(3-aminopyridin-4-yl)-2-methoxy-3-methylcyclohexyl)carbamate

HRID 879207Notes

Reaction equation

HRID 879207 reaction equation
[OH:1][C@@H:2]1[C@H:7]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH:6]=[C:5]([C:16]2[CH:21]=[CH:20][N:19]=[CH:18][C:17]=2[N+:22]([O-])=O)[CH2:4][C@@H:3]1[CH3:25].[CH3:26]C(O)C>[Pd]>[NH2:22][C:17]1[CH:18]=[N:19][CH:20]=[CH:21][C:16]=1[C@@H:5]1[CH2:6][C@H:7]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[C@H:2]([O:1][CH3:26])[C@H:3]([CH3:25])[CH2:4]1.[NH2:22][C:17]1[CH:18]=[N:19][CH:20]=[CH:21][C:16]=1[C@H:5]1[CH2:6][C@@H:7]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[C@@H:2]([O:1][CH3:26])[C@@H:3]([CH3:25])[CH2:4]1

Participants

5

Reactant 2

HCID 3776IsopropanolHCID 86705242(+/-)-Tert-butyl (1R,5S,6S)-6-hydroxy-5-methyl-3-(3-nitropyridin-4-yl)cyclohex-2-enylcarbamate

Product 2

HCID 86705255tert-butyl ((1S,2R,3R,5S)-5-(3-aminopyridin-4-yl)-2-methoxy-3-methylcyclohexyl)carbamateYield 42%HCID 86705256tert-butyl ((1R,2S,3S,5R)-5-(3-aminopyridin-4-yl)-2-methoxy-3-methylcyclohexyl)carbamateYield 39%

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

To a degassed solution of (+/−)-tert-butyl ((1R,5S,6S)-6-hydroxy-5-methyl-3-(3-nitropyridin-4-yl)cyclohex-2-en-1-yl)carbamate (1.0 equiv.) in i-PrOH (0.07 M) was added Pd/C (0.1 equiv.). The solution was degassed and purged to H2 and left stirring under a balloon of H2 at rt for 16 hrs. The solution was degassed and purged to Ar, diluted with CH2Cl2, filtered through a pad of celite, concentrated and purified by ISCO SiO2 chromatography. Purification was completed via SFC (20% MeOH, 100 mL/min, AD column) to yield tert-butyl ((1S,2R,3R,5S)-5-(3-aminopyridin-4-yl)-2-methoxy-3-methylcyclohexyl)carbamate (42% yield, 99% ee) and tert-butyl ((1R,2S,3S,5R)-5-(3-aminopyridin-4-yl)-2-methoxy-3-methylcyclohexyl)carbamate (39% yield, 99% ee). LC/MS (m/z)=336.2 (MH+), Rt=0.67 min. 1H NMR (400 MHz, <cdcl3>) δ ppm 1.08 (d, J=7.04 Hz, 3H), 1.43-1.49 (m, 10H), 1.52-1.64 (m, 2H), 1.70-1.81 (m, 2H), 2.52-2.64 (m, 1H), 3.39 (br. s., 1H), 3.52-3.57 (m, 3H), 3.62 (br. s., 2H), 3.66-3.75 (m, 1H), 4.75-4.87 (m, 1H), 6.98 (d, J=5.09 Hz, 1H), 7.95-8.05 (m, 2H).

Workup

  1. customThe solution was degassed
  2. custompurged to H2
  3. waitleft
  4. customThe solution was degassed
  5. custompurged to Ar
  6. additiondiluted with CH2Cl2
  7. filtrationfiltered through a pad of celite
  8. concentrationconcentrated
  9. custompurified by ISCO SiO2 chromatography
  10. customPurification

Sources & evidence

ORD record
ord-f29c82fb64614ef0ae454c45457aa0c7
Source dataset
uspto-grants-2015_03
Patent number
US08987457B2

Reaction notes

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