Diisopropylethylamine → (S)-2-tert-butoxycarbonylamino-4-[3-(4-chloro-phenoxy)-azetidin-1-yl]4-oxo-butyric acid benzyl ester

HRID 1182091Notes

Reaction equation

HRID 1182091 reaction equation
[CH2:1]([O:8][C:9](=[O:23])[C@@H:10]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:11][C:12]([OH:14])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.Cl.[Cl:56][C:57]1[CH:67]=[CH:66][C:60]([O:61][CH:62]2[CH2:65][NH:64][CH2:63]2)=[CH:59][CH:58]=1>ClCCl>[CH2:1]([O:8][C:9](=[O:23])[C@@H:10]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:11][C:12]([N:64]1[CH2:65][CH:62]([O:61][C:60]2[CH:59]=[CH:58][C:57]([Cl:56])=[CH:67][CH:66]=2)[CH2:63]1)=[O:14])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 7017887(3S)-4-(benzyloxy)-3-(((tert-butoxy)carbonyl)amino)-4-oxobutanoic acidHCID 573501973-(4-Chlorophenoxy)azetidine hydrochloride

Product 1

HCID 69409254(S)-2-tert-butoxycarbonylamino-4-[3-(4-chloro-phenoxy)-azetidin-1-yl]4-oxo-butyric acid benzyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (S)-2-tert-butoxycarbonylamino-succinic acid 1-benzyl ester (5.0 g, 13.99 mmol) in dichloromethane (50 ml) is treated with diisopropylethylamine (7.51 ml, 41.97 mmol) and 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyl-uronium tetrafluoroborate (4.49 g, 13.99 mmol). To the reaction mixture is added 3-(4-chloro-phenoxy)-azetidine hydrochloride (3.06 g, 13.99 mmol) and stirring continued for 3 hours. The dichloromethane is evaporated and residue partitioned between ethylacetate and saturated NaHCO3 solution. The ethylacetate phase is washed with 1M HCl solution and brine, dried over MgSO4 and evaporated. The crude product is purified by flash silica chromatography (elution with 1:1 ethylacetate/hexane) to afford (S)-2-tert-butoxycarbonylamino-4-[3-(4-chloro-phenoxy)-azetidin-1-yl]4-oxo-butyric acid benzyl ester. [M-BOC] 389.0.

Workup

  1. customThe dichloromethane is evaporated
  2. customresidue partitioned between ethylacetate and saturated NaHCO3 solution
  3. washThe ethylacetate phase is washed with 1M HCl solution and brine
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. customThe crude product is purified by flash silica chromatography (elution with 1:1 ethylacetate/hexane)

Sources & evidence

ORD record
ord-f72b4ddbd7a84ad3ab562d391c52cf9c
Source dataset
uspto-grants-2007_10
Patent number
US07288537B2

Reaction notes

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