Dimethylformamide → HCID 68325557, compound

HRID 2403323Notes

Reaction equation

HRID 2403323 reaction equation
[OH:1][C:2]1[CH:3]=[N:4][C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([C@H:15]3[O:20][CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:16]3)=[CH:11][CH:10]=2)=[N:6][CH:7]=1.C([O-])([O-])=O.[K+].[K+].CN(C=O)C.Cl[C:40]([F:47])([F:46])C(OCC)=O>CCOC(C)=O>[F:46][CH:40]([F:47])[O:1][C:2]1[CH:7]=[N:6][C:5]([NH:8][C:9]2[CH:10]=[CH:11][C:12]([C@H:15]3[O:20][CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:16]3)=[CH:13][CH:14]=2)=[N:4][CH:3]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 67843Acetic acid, 2-chloro-2,2-difluoro-, ethyl esterHCID 68325542HCID 68325542, compound

Product 1

HCID 68325557HCID 68325557, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

(R)-tert-Butyl 2-(4-(5-hydroxypyrimidin-2-ylamino)phenyl)morpholine-4-carboxylate (0.24 g) and K2CO3 (124 mg) were combined with DMF (2 ml) to give a brown solution. Ethyl 2-chloro-2,2-difluoroacetate (152 mg) was then added. The reaction mixture was stirred at 80° C. for 1.5 h to afford a dark brown suspension. TLC & HPLC showed the reaction was complete. The reaction mixture was poured into EtOAc and washed sequentially with water and with saturated brine. The organic layer was separated, dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel; gradient: 0% to 70% EtOAc in hexanes) to afford (R)-tert-butyl 2-(4-(5-(difluoromethoxy)pyrimidin-2-ylamino)phenyl)morpholine-4-carboxylate (60 mg, 24%) as a yellow oil. MS (ISP): 423.1 ([M+H]+), 367.0 ([M+H—C4H8]+).

Workup

  1. customto give a brown solution
  2. customto afford a dark brown suspension
  3. washwashed sequentially with water and with saturated brine
  4. customThe organic layer was separated
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by flash chromatography (silica gel; gradient: 0% to 70% EtOAc in hexanes)

Sources & evidence

ORD record
ord-a10e38574bd848a0b7606727b83a974a
Source dataset
uspto-grants-2014_08
Patent number
US08802673B2

Reaction notes

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