Trifluoroacetic acid → [2S,3S]-[2-[(2S)-(2-tert-butoxycarbonylamino-4-methylsulfanyl-butyrylamino)]-3-hydroxy-hex-4-ynyl]-carbamic acid benzyl ester

HRID 1391978Notes

Reaction equation

HRID 1391978 reaction equation
C(O[C:6](=[O:26])[NH:7][C@@H:8]([CH2:14][NH:15][C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17])[C@@H:9]([OH:13])[C:10]#[C:11][CH3:12])(C)(C)C.C(O)(C(F)(F)F)=O.C(N(CC)C(C)C)(C)C.C1C=CC2N(O)N=NC=2C=1.[C:53]([NH:60][C@H:61](C(O)=O)[CH2:62][CH2:63][S:64][CH3:65])([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C(Cl)Cl>[CH2:19]([O:18][C:16](=[O:17])[NH:15][CH2:14][C@H:8]([NH:7][C:6](=[O:26])[C@@H:61]([NH:60][C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[CH2:62][CH2:63][S:64][CH3:65])[C@@H:9]([OH:13])[C:10]#[C:11][CH3:12])[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

8

Reactant 6

HCID 6422Trifluoroacetic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 89857Boc-L-methionineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 67271362(2S,3S)-(2-tert-butoxycarbonylamino-3-hydroxy-hex-4-ynyl)-carbamic acid benzyl ester

Product 1

HCID 67270725[2S,3S]-[2-[(2S)-(2-tert-butoxycarbonylamino-4-methylsulfanyl-butyrylamino)]-3-hydroxy-hex-4-ynyl]-carbamic acid benzyl esterYield 78.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of [1S,2S]-[1-(Benzyloxycarbonylamino-methyl)-2-hydroxy-pent-3-ynyl]-carbamic acid tert-butyl ester (1.19 g, 3.29 mmol, prepared as described in WO PCT 0250019) was dissolved in CH2Cl2 (20 mL) and treated with TFA (10 mL). The solution was stirred for 3 h and then concentrated in vacuo. The residue was dissolved in CH2Cl2 and concentrated in vacuo; this procedure was repeated. The residue was dissolved in CH2Cl2 (30 mL). The resultant solution was charged sequentially with N, N-diisopropylethylamine (2.3 mL, 13.2 mmol), HOBt (466 mg, 3.45 mmol), N-Boc methionine (820 mg, 3.29 mmol), and BOP (1.53 g, 3.45 mmol). The reaction was stirred for 12 h and partitioned between EtOAc and sat. NH4Cl. The organic phase was washed with sat. NaHCO3 and brine, and then dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography to afford [2S,3S]-[2-[(2S)-(2-tert-butoxycarbonylamino-4-methylsulfanyl-butyrylamino)]-3-hydroxy-hex-4-ynyl]-carbamic acid benzyl ester (1.27 g, 78% yield). MS found: (M+Na)+=516.3.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in CH2Cl2
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in CH2Cl2 (30 mL)
  5. stirringThe reaction was stirred for 12 h
  6. custompartitioned between EtOAc and sat. NH4Cl
  7. washThe organic phase was washed with sat. NaHCO3 and brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-cf16a87e73e248c58d7229871cc20860
Source dataset
uspto-grants-2008_03
Patent number
US07338975B2

Reaction notes

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