N-(tert-butoxycarbonyl)glycine → {2-[(S)-2-Benzyl-4-(3-cyclopentyloxy-4-methoxy-phenyl)-piperazin-1-yl]-2-oxo-ethyl}-carbamic acid tert-butyl ester

HRID 1423121Notes

Reaction equation

HRID 1423121 reaction equation
[CH2:1]([C@@H:8]1[NH:13][CH2:12][CH2:11][N:10]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)[CH:15]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:28]([NH:35][CH2:36][C:37](O)=[O:38])([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29].C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CN(C=O)C>[C:31]([O:30][C:28](=[O:29])[NH:35][CH2:36][C:37]([N:13]1[CH2:12][CH2:11][N:10]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)[CH:15]=2)[CH2:9][C@@H:8]1[CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:38])([CH3:34])([CH3:32])[CH3:33]

Participants

6

Reactant 4

HCID 78288N-(tert-butoxycarbonyl)glycineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 16725642(S)-3-Benzyl-1-(3-cyclopentyloxy-4-methoxy-phenyl)-piperazine

Product 1

HCID 66824974{2-[(S)-2-Benzyl-4-(3-cyclopentyloxy-4-methoxy-phenyl)-piperazin-1-yl]-2-oxo-ethyl}-carbamic acid tert-butyl esterYield 81.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (S)-3-Benzyl-1-(3-cyclopentyloxy-4-methoxy-phenyl)-piperazine (73 mg, 0.2 mmol) and BOC-glycine (35 mg, 0.2 mmol) in DMF (1.0 mL) at room temperature was treated with diisopropylethylamine (35 μL, 0.2 mmol) followed by 2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) (84 mg, 0.22 mmol). The reaction mixture was stirred for 2 h then partitioned between EtOAc (10 mL) and a saturated aqueous NaHCO3 solution (10 mL). The organic component was isolated and further washed with brine (10 mL) then dried over MgSO4, filtered, and evaporated to an oil which was purified by silica gel flash chromatography with 40% EtOAc/hexane as eluant to afford intermediate {2-[(S)-2-Benzyl-4-(3-cyclopentyloxy-4-methoxy-phenyl)-piperazin-1-yl]-2-oxo-ethyl}-carbamic acid tert-butyl ester as a foam (85 mg, 81%). LC/MS 7.46 min, [M+1]+ 524.

Workup

  1. customthen partitioned between EtOAc (10 mL)
  2. customThe organic component was isolated
  3. washfurther washed with brine (10 mL)
  4. dry with materialthen dried over MgSO4
  5. filtrationfiltered
  6. customevaporated to an oil which
  7. customwas purified by silica gel flash chromatography with 40% EtOAc/hexane as eluant

Sources & evidence

ORD record
ord-30b70eea84ad446188e3552e00575a56
Source dataset
uspto-grants-2015_01
Patent number
US08927546B2

Reaction notes

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