Diisopropylethylamine → (1SR,3RS,4SR)-3-{[(5-chloro-thiophene-2-carbonyl)-amino]-methyl}-4-hydroxy-cyclopentanecarboxylic acid methyl ester

HRID 2244679Notes

Reaction equation

HRID 2244679 reaction equation
[CH3:1][O:2][C:3]([CH:5]1[CH2:9][CH:8]([OH:10])[CH:7]([CH2:11][NH2:12])[CH2:6]1)=[O:4].C(N(C(C)C)C(C)C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[Cl:49][C:50]1[S:54][C:53]([C:55](O)=[O:56])=[CH:52][CH:51]=1>CN(C=O)C.CCOC(C)=O>[CH3:1][O:2][C:3]([CH:5]1[CH2:9][CH:8]([OH:10])[CH:7]([CH2:11][NH:12][C:55]([C:53]2[S:54][C:50]([Cl:49])=[CH:51][CH:52]=2)=[O:56])[CH2:6]1)=[O:4]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 950485-Chloro-2-thiophenecarboxylic acidHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 68685423Methyl 3-(aminomethyl)-4-hydroxycyclopentane-1-carboxylate

Product 1

HCID 68687973(1SR,3RS,4SR)-3-{[(5-chloro-thiophene-2-carbonyl)-amino]-methyl}-4-hydroxy-cyclopentanecarboxylic acid methyl esterYield 32%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred suspension of the crude (1SR,3SR,4RS)-3-aminomethyl-4-hydroxy-cyclopentanecarboxylic acid methyl ester (189 mg) at r.t. in DMF (5 ml) under an argon atmosphere were added N-ethyldiisopropylamine (0.74 ml), BOP (531 mg) and 5-chloro-2-thiophenecarboxylic acid (195 mg). The reaction mixture was stirred over night, then diluted with EtOAc and washed with H2O. The aqueous phase was back extracted with EtOAc. The combined organics were washed with H2O and brine, dried (MgSO4), filtered and concentrated. The crude product was purified by column chromatography (silica gel; gradient: CH2Cl2→CH2Cl2/MeOH 93:7) to give (1SR,3SR,4RS)-3-{[(5-chloro-thiophene-2-carbonyl)-amino]-methyl}-4-hydroxy-cyclopentanecarboxylic acid methyl ester (111 mg) as light brown gum. MS: 318.0 ([M+H]+).

Workup

  1. washwashed with H2O
  2. extractionThe aqueous phase was back extracted with EtOAc
  3. washThe combined organics were washed with H2O and brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by column chromatography (silica gel; gradient: CH2Cl2→CH2Cl2/MeOH 93:7)

Sources & evidence

ORD record
ord-6fbece89f5fc4e679dd6db35d1143ca2
Source dataset
uspto-grants-2010_03
Patent number
US07678917B2

Reaction notes

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