Triphenylphosphine → (R)-tert-butyl 2-(4-chloro-3-fluorophenyl)morpholine-4-carboxylate

HRID 530590Notes

Reaction equation

HRID 530590 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([OH:21])[CH2:9][N:10]([CH2:18][CH2:19]O)[C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:4][C:3]=1[F:22].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>COC(C)(C)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[O:21][CH2:19][CH2:18][N:10]([C:11]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:17])[CH2:9]2)=[CH:4][C:3]=1[F:22]

Participants

5

Reactant 3

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 117872015(R)-tert-butyl2-(4-chloro-3-fluorophenyl)-2-hydroxyethyl(2-hydroxyethyl)carbamate

Product 1

HCID 118276753(R)-tert-butyl 2-(4-chloro-3-fluorophenyl)morpholine-4-carboxylateYield 43.1%

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

Procedure

(R)-tert-butyl 2-(4-chloro-3-fluorophenyl)-2-hydroxyethyl(2-hydroxyethyl)carbamate (2.5 g, 7.49 mmol) was dissolved in methyl-t-butylether (20 mL) and triphenylphosphine (2.36 g, 8.99 mmol) was added. To this mixture was added diisopropyl azodicarboxylate (1.8 mL, 8.99 mmol) by dropwise addition. The solution was stirred at room temperature for 1 h. The white solid was filtered off and the filtrate was concentrated. The residue was purified by ISCO flash column chromatography (220 g silica gel, 0% to 20% ethyl acetate in hexanes) to afford (R)-tert-butyl 2-(4-chloro-3-fluorophenyl)morpholine-4-carboxylate as a white solid (1.02 g). 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.49 (s, 9H) 2.75 (t, J=11.71 Hz, 1H) 2.94-3.11 (m, 1H) 3.67 (td, J=11.71, 3.02 Hz, 1H) 3.86-4.17 (m, 3H) 4.40 (dd, J=10.58, 2.64 Hz, 1H) 7.09 (dd, J=8.31, 1.51 Hz, 1H) 7.21 (dd, J=9.82, 1.89 Hz, 1H) 7.38 (t, J=7.93 Hz, 1H).

Workup

  1. additionby dropwise addition
  2. filtrationThe white solid was filtered off
  3. concentrationthe filtrate was concentrated
  4. customThe residue was purified by ISCO flash column chromatography (220 g silica gel, 0% to 20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-16aa3b88bc6a4124b3429dfb41027358
Source dataset
uspto-grants-2016_05
Patent number
US09353096B2

Reaction notes

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