Diisopropylethylamine → (S)-tert-butyl 4-(tert-butoxycarbonylamino)-4-(1-(4-chlorophenyl)-3-hydroxypropylcarbamoyl)piperidine-1-carboxylate

HRID 423067Notes

Reaction equation

HRID 423067 reaction equation
[NH2:1][C@H:2]([C:6]1[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][CH:7]=1)[CH2:3][CH2:4][OH:5].[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][C:23]([NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])([C:26](O)=[O:27])[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CC(N(C)C)=O>[C:33]([O:32][C:30]([NH:29][C:23]1([C:26](=[O:27])[NH:1][C@H:2]([C:6]2[CH:7]=[CH:8][C:9]([Cl:12])=[CH:10][CH:11]=2)[CH2:3][CH2:4][OH:5])[CH2:22][CH2:21][N:20]([C:18]([O:17][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:19])[CH2:25][CH2:24]1)=[O:31])([CH3:36])([CH3:35])[CH3:34]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 12682251-(tert-Butoxycarbonyl)-4-((tert-butoxycarbonyl)amino)piperidine-4-carboxylic acid2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 25418153(3S)-3-amino-3-(4-chlorophenyl)propan-1-ol2×

Product 1

HCID 57750274(S)-tert-butyl 4-(tert-butoxycarbonylamino)-4-(1-(4-chlorophenyl)-3-hydroxypropylcarbamoyl)piperidine-1-carboxylateYield 155%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
20 °C

Procedure

(S)-3-amino-3-(4-chlorophenyl)propan-1-ol (Intermediate 47) (1.09 g, 5.87 mmol) was added in one portion to 1-(tert-butoxycarbonyl)-4-(tert-butoxycarbonylamino)piperidine-4-carboxylic acid (Intermediate 70) (2.022 g, 5.87 mmol) and DIPEA (3.08 mL, 17.61 mmol) in DMA (20 mL). O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (2.456 g, 6.46 mmol) was added and the resulting solution was stirred at 20° C. for 24 hours. The reaction mixture was evaporated to dryness then diluted with EtOAc (300 mL), and washed sequentially with water (50 mL) and saturated brine (50 mL). The organic layer was dried over MgSO4, filtered and evaporated then triturated with diethyl ether to afford crude (S)-tert-butyl 4-(tert-butoxycarbonylamino)-4-(1-(4-chlorophenyl)-3-hydroxypropylcarbamoyl)piperidine-1-carboxylate (4.66 g, 155%) as a white solid.

Workup

  1. customThe reaction mixture was evaporated to dryness
  2. additionthen diluted with EtOAc (300 mL)
  3. washwashed sequentially with water (50 mL) and saturated brine (50 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customthen triturated with diethyl ether

Sources & evidence

ORD record
ord-b79b3003cbbb48c6943430e6e1e3ba5c
Source dataset
uspto-grants-2012_01
Patent number
US08101623B2

Reaction notes

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