Triphenylphosphine → HCID 59451538, compound

HRID 1874790Notes

Reaction equation

HRID 1874790 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([O-:13])=[O:12])=[CH:5]2.[C:14]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.O[CH2:46][C@@H:47]1[O:52][CH2:51][CH2:50][N:49]([C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[CH2:48]1>C(Cl)Cl>[CH3:57][C:56]([O:55][C:53]([N:49]1[CH2:50][CH2:51][O:52][C@@H:47]([CH2:46][O:1][C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][C:6]([C:11]([O:13][CH3:14])=[O:12])=[CH:5]3)[CH2:48]1)=[O:54])([CH3:59])[CH3:58]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 1512576(R)-N-Boc-2-hydroxymethylmorpholineHCID 178524047HCID 178524047, compound

Product 1

HCID 59451538HCID 59451538, compoundYield 76.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methyl 5-{[((2R)-4-{[(1,1-dimethylethyl)oxy]carbonyl}-2-morpholinyl)methyl]oxy}-1H-indole-2-carboxylate was prepared in a similar manner as described herein from 5-hydroxy-1H-indole-2-carboxylate (0.10 g, 0.5 mmol), triphenylphosphine (0.28 g, 1.0 mmol), diethyl azodicarboxylate (0.18 g, 1.0 mmol), 1,1-dimethylethyl (2R)-2-(hydroxymethyl)-4-morpholinecarboxylate (0.23 g, 1.0 mmol) and CH2Cl2 (5 mL). The crude material was purified by Reverse-Phase HPLC (water/acetonitrile with 0.1% TFA). The desired fractions were neutralized and extracted with EtOAc. The organic extracts were combined, dried over Na2SO4, filtered and evaporated to afford the title compound (0.15 g, 73%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 11.76 (s, 1H), 7.30 (d, 1H), 7.08 (d, 1H), 7.00 (d, 1H), 6.89 (dd, 1H), 3.94 (d, 2H), 3.81 (s, 3H), 3.78-3.92 (m, 2H), 3.59-3.73 (m, 2H), 3.35-3.46 (m, 1H), 2.76-2.97 (m, 2H), 1.36 (s, 9H)MS: m/z 391.2 (M+1).

Workup

  1. customMethyl 5-{[((2R)-4-{[(1,1-dimethylethyl)oxy]carbonyl}-2-morpholinyl)methyl]oxy}-1H-indole-2-carboxylate was prepared in a similar manner
  2. customThe crude material was purified by Reverse-Phase HPLC (water/acetonitrile with 0.1% TFA)
  3. extractionextracted with EtOAc
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-9327e612a4204e4a8098b4cf3b1d2360
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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