tert-Butyl carbamate → (RS)-4-{1-[5-(4-Fluorophenyl)-2-methylthiazol-4-yl]-methanoyl}-3-[4-(4-fluoro-phenyl)-oxazol-2-ylmethyl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 30189Notes

Reaction equation

HRID 30189 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([C:16]2[N:17]=[C:18]([CH3:28])[S:19][C:20]=2[C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)=[O:15])[CH:10]([CH2:29][C:30]([O:32][CH2:33][C:34]([C:36]2[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=2)=O)=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)(OC(C)(C)C)[NH2:44]>B(F)(F)F.CCOCC.C1(C)C(C)=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([C:16]2[N:17]=[C:18]([CH3:28])[S:19][C:20]=2[C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)=[O:15])[CH:10]([CH2:29][C:30]2[O:32][CH:33]=[C:34]([C:36]3[CH:37]=[CH:38][C:39]([F:42])=[CH:40][CH:41]=3)[N:44]=2)[CH2:9]1)=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

5

Reactant 2

HCID 77922tert-Butyl carbamateHCID 67158091(RS)-4-{1-[5-(4-Fluorophenyl)-2-methylthiazol-4-yl]-methanoyl}-3-[2-(4-fluoro-phenyl)-2-oxo-ethoxycarbonylmethyl]-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 67157954(RS)-4-{1-[5-(4-Fluorophenyl)-2-methylthiazol-4-yl]-methanoyl}-3-[4-(4-fluoro-phenyl)-oxazol-2-ylmethyl]-piperazine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 8000Boron trifluoride etherateCatalystHCID 7237O-XyleneSolvent

Conditions

Temperature
140 °C

Procedure

(RS)-4-{1-[5(4-Fluorophenyl)-2-methylthiazol4-yl]-methanoyl}-3-[2-(4-fluoro-phenyl)-2-oxo-ethoxycarbonylmethyl]-piperazine-1-carboxylic acid tert-butyl ester, description 111 (0.385 g), tert-butyl carbamate (0.376 g) and boron trifluoride etherate (4 drops) were dissolved in xylene (5 ml) and heated to 140° C., under argon and with stirring for 48 hours. After cooling, the reaction mixture was partitioned between ethyl acetate and saturated sodium hydrogen carbonate solution. The organic layer was dried (MgSO4), evaporated and the residue chromatographed over silica gel. Elution with a gradient of 25 to 100% ethyl acetate in hexane provided the title compound as a pale yellow oil (0.130 g), mass spectrum (API+) 581 [MH+], C30H30F2N4O4S requires 580.

Workup

  1. temperatureAfter cooling
  2. customthe reaction mixture was partitioned between ethyl acetate and saturated sodium hydrogen carbonate solution
  3. dry with materialThe organic layer was dried (MgSO4)
  4. customevaporated
  5. customthe residue chromatographed over silica gel
  6. washElution with a gradient of 25 to 100% ethyl acetate in hexane

Sources & evidence

ORD record
ord-d64e549efc304b568e4317bed850a737
Source dataset
uspto-grants-2008_09
Patent number
US07423052B2

Reaction notes

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