Diisopropylamine → ethyl 9-benzyloxy-5(S)-tert-butoxycarbonylamino-4(R,S)-hydroxy-7,7-dimethyl-non-2-inoate

HRID 863274Notes

Reaction equation

HRID 863274 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[C:13]([O:17][CH2:18][CH3:19])(=[O:16])[C:14]#[CH:15].[CH2:20]([O:27][CH2:28][CH2:29][C:30]([CH3:44])([CH3:43])[CH2:31][C@H:32]([NH:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH:33]=[O:34])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>CCCCCC.O1CCCC1>[CH2:20]([O:27][CH2:28][CH2:29][C:30]([CH3:44])([CH3:43])[CH2:31][C@H:32]([NH:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH:33]([OH:34])[C:15]#[C:14][C:13]([O:17][CH2:18][CH3:19])=[O:16])[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 12182Ethyl propiolateHCID 228825796-Benzyloxy-2(S)-tert-butoxycarbonylamino-4,4-dimethyl-hexanalHCID 178418339Butyllithium

Product 1

HCID 131720520ethyl 9-benzyloxy-5(S)-tert-butoxycarbonylamino-4(R,S)-hydroxy-7,7-dimethyl-non-2-inoate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Procedure

22.2 ml of a 1.6M n-butyllithium solution in hexane are added to a solution of 5.1 ml of diisopropylamine in 40 ml of tetrahydrofuran at -78° C. under argon, while stirring. After 30 min, a solution, cooled to -78° C., of 2.5 ml of ethyl propiolate in 20 ml of tetrahydrofuran is added dropwise via a cannula. The yellow reaction solution is stirred at -78° C. for a further 1 h and 5.0 g of 6-benzyloxy-2(S)-tert-butoxycarbonylamino-4,4-dimethyl-hexanal (Example 390) in 30 ml of tetrahydrofuran are then added dropwise. After the mixture has been stirred for 4.5 h, the reaction is quenched by addition of saturated aqueous ammonium chloride solution and the reaction mixture is allowed to warm to room temperature and is worked up in the customary manner. The crude product is purified by FC over silica gel (eluting agent C). The title compound is obtained as a mixture of the 4(S) and 4(R) diastereomers in a ratio of about (5.4:1): Rf (C)=0.28; FAB-MS: (M+H)+ =448.

Workup

  1. additionis added dropwise via a cannula
  2. stirringThe yellow reaction solution is stirred at -78° C. for a further 1 h
  3. stirringAfter the mixture has been stirred for 4.5 h
  4. customthe reaction is quenched by addition of saturated aqueous ammonium chloride solution
  5. customThe crude product is purified by FC over silica gel (eluting agent C)

Sources & evidence

ORD record
ord-81f4d465f5c34d4cbf1c34ae0b02a007
Source dataset
uspto-grants-1998_02
Patent number
US05719141

Reaction notes

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