Methanol → (3S,4R)-3-Hydroxymethyl-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1158333

反応式

HRID 1158333 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH:31]([CH3:33])[CH3:32])[C:15](=[O:30])[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH2:25][CH2:26][CH2:27][O:28][CH3:29])[CH:17]=2)[C@H:10]([C:34](O)=[O:35])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CSC.B.CO>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH:31]([CH3:32])[CH3:33])[C:15](=[O:30])[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH2:25][CH2:26][CH2:27][O:28][CH3:29])[CH:17]=2)[C@H:10]([CH2:34][OH:35])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

5

反応物 3

HCID 887MethanolHCID 12423031(Dimethyl sulfide)trihydroboronHCID 59512388(3S*,4R*)-4-({Isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester

生成物 1

HCID 59512299(3S,4R)-3-Hydroxymethyl-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-10 °C

実験手順

To a solution of (3S*,4R*)-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester (1.29 g, 2.54 mmol) (Example 1 G) in THF (25 mL), a solution of borane dimethylsulfide complex (2M in THF, 2.80 mL, 5.58 mmol) is slowly added at −10° C. The mixture is stirred for 20 min at −10° C., then allowed to reach RT and further stirred overnight. MeOH is carefully added (exothermic!), and the mixture is concentrated under reduced pressure. MeOH is again added, and the mixture is concentrated. This operation is repeated 3 times, and the mixture is finally taken up into a saturated aqueous solution of NaHCO3 and extracted 3 times with CH2Cl2. The combined organic extracts are dried over Na2SO4, filtered and concentrated. The crude material is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH from 100:0 to 95:5) to give the desired product. TLC, Rf (CH2Cl2/MeOH 95:5)=0.3. MS (LC-MS): 395.1 [M+H-Boc]+; tR (HPLC, C18 column, 10-100% CH3CN/H2O/5 min, 100% CH3CN/3 min, CH3CN and H2O containing 0.1% TFA, flow: 1.5 mL/min): 5.01 min.

後処理

  1. waitto reach RT and further stirred overnight
  2. concentrationthe mixture is concentrated under reduced pressure
  3. additionMeOH is again added
  4. concentrationthe mixture is concentrated
  5. extractionextracted 3 times with CH2Cl2
  6. dry with materialThe combined organic extracts are dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH from 100:0 to 95:5)

出典と根拠

ORDレコード
ord-5e5fba82ad7049798db11866dc87b651
出典データセット
uspto-grants-2010_10
特許番号
US07807709B2

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