Aluminium lithium hydride → (S)-tert-butyl 4-(1-(4-chlorophenyl)-3-hydroxypropylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate

HRID 423041Notes

Reaction equation

HRID 423041 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[C:7]([O:11][C:12]([NH:14][C:15]1([C:30]([NH:32][C@H:33]([C:39]2[CH:44]=[CH:43][C:42]([Cl:45])=[CH:41][CH:40]=2)[CH2:34][C:35](OC)=[O:36])=[O:31])[CH2:20][CH2:19][N:18]([C:21]2[C:22]3[CH:29]=[CH:28][NH:27][C:23]=3[N:24]=[CH:25][N:26]=2)[CH2:17][CH2:16]1)=[O:13])([CH3:10])([CH3:9])[CH3:8]>C1COCC1>[Cl:45][C:42]1[CH:41]=[CH:40][C:39]([C@@H:33]([NH:32][C:30]([C:15]2([NH:14][C:12](=[O:13])[O:11][C:7]([CH3:9])([CH3:8])[CH3:10])[CH2:16][CH2:17][N:18]([C:21]3[C:22]4[CH:29]=[CH:28][NH:27][C:23]=4[N:24]=[CH:25][N:26]=3)[CH2:19][CH2:20]2)=[O:31])[CH2:34][CH2:35][OH:36])=[CH:44][CH:43]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 57750405(S)-methyl 3-(4-(tert-butoxycarbonylamino)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamido)-3-(4-chlorophenyl)propanoate2×

Product 1

HCID 57750298(S)-tert-butyl 4-(1-(4-chlorophenyl)-3-hydroxypropylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamateYield 86.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

LiAlH4 (2.280 mL, 2.28 mmol) was added dropwise to (S)-methyl 3-(4-(tert-butoxycarbonylamino)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamido)-3-(4-chlorophenyl)propanoate (Intermediate 21) (1.27 g, 2.28 mmol) in THF (70 mL) cooled to 0° C. under nitrogen. The resulting solution was stirred at 20° C. for 1 hour. The reaction mixture was quenched with sodium hydroxide (2M) (2 mL) and water (1 mL). The solution was filtered and was diluted with EtOAc (200 mL), and washed sequentially with water (100 mL), water (100 mL), and saturated brine (100 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford (S)-tert-butyl 4-(1-(4-chlorophenyl)-3-hydroxypropylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate (1.04 g, 86%) as a white solid. M/z (ESI+) (M+H)+=529; HPLC tR=2.00 min.

Workup

  1. customThe reaction mixture was quenched with sodium hydroxide (2M) (2 mL) and water (1 mL)
  2. filtrationThe solution was filtered
  3. additionwas diluted with EtOAc (200 mL)
  4. washwashed sequentially with water (100 mL), water (100 mL), and saturated brine (100 mL)
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-021dccc399934a31bec657e8c61ee0e2
Source dataset
uspto-grants-2012_01
Patent number
US08101623B2

Reaction notes

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