Potassium Carbonate → tert-butyl octahydro-1H-pyrido[3,4-b][1,4]oxazine-1-carboxylate

HRID 81118Notes

Reaction equation

HRID 81118 reaction equation
FC(F)(F)C([N:5]1[CH2:14][CH2:13][C@@H:12]2[C@H:7]([O:8][CH2:9][CH2:10][N:11]2[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:6]1)=O.C([O-])([O-])=O.[K+].[K+]>CO.O>[N:11]1([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10][CH2:9][O:8][CH:7]2[CH2:6][NH:5][CH2:14][CH2:13][CH:12]12

Participants

5

Reactant 2

HCID 11430Potassium CarbonateHCID 90236069HCID 90236069, compound

Product 1

HCID 71305972tert-butyl octahydro-1H-pyrido[3,4-b][1,4]oxazine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of trans-tert-butyl 6-(trifluoroacetyl)octahydro-1H-pyrido[3,4-b][1,4]oxazine-1-carboxylate (70 g, 0.20 mol) in MeOH (160 mL) and water (600 mL) was added K2CO3 (34.2 g, 0.24 mol) in one portion at room temperature. The mixture was stirred for 2 h at room temperature, and then extracted with DCM (200 mL×5). The combined organic layers were concentrated to give tert-butyl octahydro-1H-pyrido[3,4-b][1,4]oxazine-1-carboxylate as a mixture of trans diastereomers. SFC purification afforded the pure S,S diastereomer tert-butyl (4aS,8aS)-octahydro-1H-pyrido[3,4-b][1,4]oxazine-1-carboxylate (peak 1) 1H NMR: (CDCl3) δ 3.88-3.80 (m, 2H), 3.77-3.67 (m, 1H), 3.35-3.34 (m, 2H), 3.29-3.27 (m, 2H), 3.10-3.11 (d, 1H), 2.54-2.42 (m, 3H), 1.76 (s, 1H), 1.70-1.60 (m, 1H), 1.45 (s, 9H) LCMS (M+H)=243 and R,R diastereomer tert-butyl (4aR,8aR)-octahydro-1H-pyrido[3,4-b][1,4]oxazine-1-carboxylate (peak 2)1H NMR: (CDCl3) δ 3.89-3.80 (m, 2H), 3.77-3.67 (m, 1H), 3.35-3.34 (m, 2H), 3.29-3.27 (m, 2H), 3.10-3.11 (d, 1H), 2.54-2.42 (m, 3H), 1.76 (s, 1H), 1.70-1.60 (m, 1H), 1.44 (s, 9H) LCMS (M+H)=243.

Workup

  1. extractionextracted with DCM (200 mL×5)
  2. concentrationThe combined organic layers were concentrated

Sources & evidence

ORD record
ord-19e31b196331448f9fd96ec8729f9571
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

Loading…